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Annotation and functional characterization of long noncoding RNAs deregulated in pancreatic adenocarcinoma

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Abstract

Purpose

Transcriptome analysis of pancreatic ductal adenocarcinoma (PDAC) has been useful to identify gene expression changes that sustain malignant phenotypes. Yet, most studies examined only tumor tissues and focused on protein-coding genes, leaving long non-coding RNAs (lncRNAs) largely underexplored.

Methods

We generated total RNA-Seq data from patient-matched tumor and nonmalignant pancreatic tissues and implemented a computational pipeline to survey known and novel lncRNAs. siRNA-mediated knockdown in tumor cell lines was performed to assess the contribution of PDAC-associated lncRNAs to malignant phenotypes. Gene co-expression network and functional enrichment analyses were used to assign deregulated lncRNAs to biological processes and molecular pathways.

Results

We detected 9,032 GENCODE lncRNAs as well as 523 unannotated lncRNAs, including transcripts significantly associated with patient outcome. Aberrant expression of a subset of novel and known lncRNAs was confirmed in patient samples and cell lines. siRNA-mediated knockdown of a subset of these lncRNAs (LINC01559, LINC01133, CCAT1, LINC00920 and UCA1) reduced cell proliferation, migration and invasion. Gene co-expression network analysis associated PDAC-deregulated lncRNAs with diverse biological processes, such as cell adhesion, protein glycosylation and DNA repair. Furthermore, UCA1 knockdown was shown to specifically deregulate co-expressed genes involved in DNA repair and to negatively impact DNA repair following damage induced by ionizing radiation.

Conclusions

Our study expands the repertoire of lncRNAs deregulated in PDAC, thereby revealing novel candidate biomarkers for patient risk stratification. It also provides a roadmap for functional assays aimed to characterize novel mechanisms of action of lncRNAs in pancreatic cancer, which could be explored for therapeutic development.

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Data availability

All data analyzed during this study are included in this article and its supplementary information files. Raw and processed RNA-Seq data are available at the NCBI-GEO repository under accession GSE130688. The complete annotations of the lncRNAs detected in the PDAC transcriptome and discussed in the article are provided as supplementary material (Table S4).

Change history

  • 03 September 2022

    The original online version of this article was revised: The citation information for author name Fabio Luis Forti was corrected.

References

  1. D.P. Ryan, T.S. Hong, N. Bardeesy, Pancreatic adenocarcinoma. N. Engl. J. Med. 371, 1039–1049 (2014)

    Article  CAS  PubMed  Google Scholar 

  2. P. Rawla, T. Sunkara, V. Gaduputi, Epidemiology of pancreatic cancer: Global trends, etiology and risk factors. World J. Oncol. 10, 10–27 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  3. L. Rahib, B.D. Smith, R. Aizenberg, A.B. Rosenzweig, J.M. Fleshman, L.M. Matrisian, Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74, 2913–2921 (2014)

    Article  CAS  PubMed  Google Scholar 

  4. J. Kleeff, M. Korc, M. Apte, C. La Vecchia, C.D. Johnson, A.V. Biankin, R.E. Neale, M. Tempero, D.A. Tuveson, R.H. Hruban, J.P. Neoptolemos, Pancreatic cancer. Nat. Rev. Dis. Prim. 2, 16022 (2016)

    Article  PubMed  Google Scholar 

  5. C.A. Iacobuzio-Donahue, A. Maitra, G.L. Shen-Ong, T. van Heek, R. Ashfaq, R. Meyer, K. Walter, K. Berg, M.A. Hollingsworth, J.L. Cameron, C.J. Yeo, S.E. Kern, M. Goggins, R.H. Hruban, Discovery of novel tumor markers of pancreatic cancer using global gene expression technology. Am. J. Pathol. 160, 1239–1249 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. C.D. Logsdon, D.M. Simeone, C. Binkley, T. Arumugam, J.K. Greenson, T.J. Giordano, D.E. Misek, R. Kuick, S. Hanash, Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res. 63, 2649–2657 (2003)

    CAS  PubMed  Google Scholar 

  7. S. Jones, X. Zhang, D.W. Parsons, J.C.-H. Lin, R.J. Leary, P. Angenendt, P. Mankoo, H. Carter, H. Kamiyama, A. Jimeno, S.-M. Hong, B. Fu, M.-T. Lin, E.S. Calhoun, M. Kamiyama, K. Walter, T. Nikolskaya, Y. Nikolsky, J. Hartigan, D.R. Smith, M. Hidalgo, S.D. Leach, A.P. Klein, E.M. Jaffee, M. Goggins, A. Maitra, C. Iacobuzio-Donahue, J.R. Eshleman, S.E. Kern, R.H. Hruban, R. Karchin, N. Papadopoulos, G. Parmigiani, B. Vogelstein, V.E. Velculescu, K.W. Kinzler, Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801–1806 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. J. Wang, L. Dumartin, A. Mafficini, P. Ulug, A. Sangaralingam, N.A. Alamiry, T.P. Radon, R. Salvia, R.T. Lawlor, N.R. Lemoine, A. Scarpa, C. Chelala, T. Crnogorac-Jurcevic, Splice variants as novel targets in pancreatic ductal adenocarcinoma. Sci. Rep. 7, 2980 (2017)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. E.A. Collisson, A. Sadanandam, P. Olson, W.J. Gibb, M. Truitt, S. Gu, J. Cooc, J. Weinkle, G.E. Kim, L. Jakkula, H.S. Feiler, A.H. Ko, A.B. Olshen, K.L. Danenberg, M.A. Tempero, P.T. Spellman, D. Hanahan, J.W. Gray, Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat. Med. 17, 500–503 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. R.A. Moffitt, R. Marayati, E.L. Flate, K.E. Volmar, S.G.H. Loeza, K.A. Hoadley, N.U. Rashid, L.A. Williams, S.C. Eaton, A.H. Chung, J.K. Smyla, J.M. Anderson, H.J. Kim, D.J. Bentrem, M.S. Talamonti, C.A. Iacobuzio-Donahue, M.A. Hollingsworth, J.J. Yeh, Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat. Genet. 47, 1168–1178 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. P. Bailey, D.K. Chang, K. Nones, A.L. Johns, A.-M.M. Patch, M.-C.C. Gingras, D.K. Miller, A.N. Christ, T.J.C.C. Bruxner, M.C. Quinn, C. Nourse, L.C. Murtaugh, I. Harliwong, S. Idrisoglu, S. Manning, E. Nourbakhsh, S. Wani, L. Fink, O. Holmes, V. Chin, M.J. Anderson, S. Kazakoff, C. Leonard, F. Newell, N.N.N.N.N. Waddell, S. Wood, Q. Xu, P.J. Wilson, N. Cloonan, K.S. Kassahn, D. Taylor, K. Quek, A. Robertson, L. Pantano, L. Mincarelli, L.N. Sanchez, L. Evers, J. Wu, M. Pinese, M.J. Cowley, M.D. Jones, E.K. Colvin, A.M. Nagrial, E.S. Humphrey, L.A. Chantrill, A. Mawson, J. Humphris, A. Chou, M. Pajic, C.J. Scarlett, A.V. Pinho, M. Giry-Laterriere, I. Rooman, J.S. Samra, J.G. Kench, J.A. Lovell, N.D. Merrett, C.W. Toon, K. Epari, N.Q. Nguyen, A. Barbour, N. Zeps, K. Moran-Jones, N.B. Jamieson, J.S. Graham, F. Duthie, K. Oien, J. Hair, R. Grützmann, A. Maitra, C.A. Iacobuzio-Donahue, C.L. Wolfgang, R.A. Morgan, R.T. Lawlor, V. Corbo, C. Bassi, B. Rusev, P. Capelli, R. Salvia, G. Tortora, D. Mukhopadhyay, G.M. Petersen, D.M. Munzy, W.E. Fisher, S.A. Karim, J.R. Eshleman, R.H. Hruban, C. Pilarsky, J.P. Morton, O.J. Sansom, A. Scarpa, E.A. Musgrove, U.-M.H.M.H. Bailey, O. Hofmann, R.L. Sutherland, D.A. Wheeler, A.J. Gill, R.A. Gibbs, J.V. Pearson, N.N.N.N.N. Waddell, A.V. Biankin, S.M. Grimmond, Australian Pancreatic Cancer Genome Initiative, D.M. Munzy, W.E. Fisher, S.A. Karim, J.R. Eshleman, R.H. Hruban, C. Pilarsky, J.P. Morton, O.J. Sansom, A. Scarpa, E.A. Musgrove, U.-M.H.M.H. Bailey, O. Hofmann, R.L. Sutherland, D.A. Wheeler, A.J. Gill, R.A. Gibbs, J.V. Pearson, N.N.N.N.N. Waddell, A.V. Biankin, S.M. Grimmond, Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531, 47–52 (2016)

    Article  CAS  PubMed  Google Scholar 

  12. B.J. Raphael, R.H. Hruban, A.J. Aguirre, R.A. Moffitt, J.J. Yeh, C. Stewart, A.G. Robertson, A.D. Cherniack, M. Gupta, G. Getz, S.B. Gabriel, M. Meyerson, C. Cibulskis, S.S. Fei, T. Hinoue, H. Shen, P.W. Laird, S. Ling, Y. Lu, G.B. Mills, R. Akbani, P. Loher, E.R. Londin, I. Rigoutsos, A.G. Telonis, E.A. Gibb, A. Goldenberg, A.M. Mezlini, K.A. Hoadley, E. Collisson, E. Lander, B.A. Murray, J. Hess, M. Rosenberg, L. Bergelson, H. Zhang, J. Cho, G. Tiao, J. Kim, D. Livitz, I. Leshchiner, B. Reardon, E. Van Allen, A. Kamburov, R. Beroukhim, G. Saksena, S. E. Schumacher, M.S. Noble, D.I. Heiman, N. Gehlenborg, J.Kim, M.S. Lawrence, V. Adsay, G. Petersen, D. Klimstra, N. Bardeesy, M.D.M. Leiserson, R. Bowlby, K. Kasaian, I. Birol, K.L. Mungall, S. Sadeghi, J.N. Weinstein, P.T. Spellman, Y. Liu, L.T. Amundadottir, J. Tepper, A.D. Singhi, R. Dhir, D. Paul, T. Smyrk, L. Zhang, P. Kim, J. Bowen, J. Frick, J.M. Gastier-Foster, M. Gerken, K. Lau, K.M. Leraas, T.M. Lichtenberg, N.C. Ramirez, J. Renkel, M. Sherman, L. Wise, P. Yena, E. Zmuda, J. Shih, A. Ally, M. Balasundaram, R. Carlsen, A. Chu, E. Chuah, A. Clarke, N. Dhalla, R.A. Holt, S.J.M. Jones, D. Lee, Y. Ma, M.A. Marra, M. Mayo, R.A. Moore, A.J. Mungall, J.E. Schein, P. Sipahimalani, A. Tam, N. Thiessen, K. Tse, T. Wong, D. Brooks, J.T. Auman, S. Balu, T. Bodenheimer, D.N. Hayes, A.P. Hoyle, S.R. Jefferys, C.D. Jones, S. Meng, P.A. Mieczkowski, L.E. Mose, C.M. Perou, A.H. Perou, J. Roach, Y. Shi, J.V. Simons, T. Skelly, M.G. Soloway, D. Tan, U. Veluvolu, J.S. Parker, M.D. Wilkerson, A. Korkut, Y. Senbabaoglu, P. Burch, R. McWilliams, K. Chaffee, A. Oberg, W. Zhang, M.C. Gingras, D.A. Wheeler, L. Xi, M. Albert, J. Bartlett, H. Sekhon, Y. Stephen, Z. Howard, M. Judy, A. Breggia, R.T. Shroff, S. Chudamani, J. Liu, L. Lolla, R. Naresh, T. Pihl, Q. Sun, Y. Wan, Y. Wu, S. Jennifer, K. Roggin, K.F. Becker, M. Behera, J. Bennett, L. Boice, E. Burks, C.G. Carlotti Junior, J. Chabot, D. Pretti da Cunha Tirapelli, J. Sebastião dos Santos, M. Dubina, J. Eschbacher, M. Huang, L. Huelsenbeck-Dill, R. Jenkins, A. Karpov, R. Kemp, V. Lyadov, S. Maithel, G. Manikhas, E. Montgomery, H. Noushmehr, A. Osunkoya, T. Owonikoko, O. Paklina, O. Potapova, S. Ramalingam, W.K. Rathmell, K. Rieger-Christ, C. Saller, G. Setdikova, A. Shabunin, G. Sica, T. Su, T. Sullivan, P. Swanson, K. Tarvin, M. Tavobilov, L.B. Thorne, S. Urbanski, O. Voronina, T. Wang, D. Crain, E. Curley, J. Gardner, D. Mallery, S. Morris, J. Paulauskis, R. Penny, C. Shelton, T. Shelton, K.P. Janssen, O. Bathe, N. Bahary, J. Slotta-Huspenina, A. Johns, H. Hibshoosh, R.F. Hwang, A. Sepulveda, A. Radenbaugh, S.B. Baylin, M. Berrios, M. S. Bootwalla, A. Holbrook, P.H. Lai, D.T. Maglinte, S. Mahurkar, T.J. Triche, D.J. Van Den Berg, D.J. Weisenberger, L. Chin, R. Kucherlapati, M. Kucherlapati, A. Pantazi, P. Park, G. Saksena, D. Voet, P. Lin, S. Frazer, T. Defreitas, S. Meier, L. Chin, S.Y. Kwon, Y.H. Kim, S.J. Park, S.S. Han, S.H. Kim, H. Kim, E. Furth, M. Tempero, C. Sander, A. Biankin, D. Chang, P. Bailey, A. Gill, J. Kench, S. Grimmond, A. Johns, A.P. Cancer Genome Initiative (APGI, R. Postier, R. Zuna, H. Sicotte, J.A. Demchok, M.L. Ferguson, C.M. Hutter, K.R. Mills Shaw, M. Sheth, H.J. Sofia, R. Tarnuzzer, Z. Wang, L. Yang, J. (Julia) Zhang, I. Felau, and J.C. Zenklusen. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell 32, 185–203.e13 (2017)

  13. J.E. Moore, M.J. Purcaro, H.E. Pratt, C.B. Epstein, N. Shoresh, J. Adrian, T. Kawli, C.A. Davis, A. Dobin, R. Kaul, J. Halow, E.L. Van Nostrand, P. Freese, D.U. Gorkin, Y. Shen, Y. He, M. Mackiewicz, F. Pauli-Behn, B.A. Williams, A. Mortazavi, C.A. Keller, X.-O. Zhang, S.I. Elhajjajy, J. Huey, D.E. Dickel, V. Snetkova, X. Wei, X. Wang, J.C. Rivera-Mulia, J. Rozowsky, J. Zhang, S.B. Chhetri, J. Zhang, A. Victorsen, K.P. White, A. Visel, G.W. Yeo, C.B. Burge, E. Lécuyer, D.M. Gilbert, J. Dekker, J. Rinn, E.M. Mendenhall, J.R. Ecker, M. Kellis, R.J. Klein, W.S. Noble, A. Kundaje, R. Guigó, P.J. Farnham, J.M. Cherry, R.M. Myers, B. Ren, B.R. Graveley, M.B. Gerstein, L.A. Pennacchio, M.P. Snyder, B.E. Bernstein, B. Wold, R.C. Hardison, T.R. Gingeras, J.A. Stamatoyannopoulos, Z. Weng, and T. E. P. Consortium, Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583, 699–710 (2020)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. M. Huarte, The emerging role of LncRNAs in cancer. Nat. Med. 21, 1253–1261 (2015)

    Article  CAS  PubMed  Google Scholar 

  15. J.L. Rinn, H.Y. Chang, Long noncoding RNAs: Molecular modalities to organismal functions. Annu. Rev. Biochem. 89, 283–308 (2020)

    Article  CAS  PubMed  Google Scholar 

  16. S.U. Schmitz, P. Grote, B.G. Herrmann, Mechanisms of long noncoding RNA function in development and disease. Cell. Mol. Life Sci. 73, 2491–2509 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. G. Xiong, S. Pan, J. Jin, X. Wang, R. He, F. Peng, X. Li, M. Wang, J. Zheng, F. Zhu, R. Qin, Long noncoding competing endogenous RNA networks in pancreatic cancer. Front. Oncol. 11, 765216 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  18. R. Gong, Y. Jiang, Non-coding RNAs in pancreatic ductal adenocarcinoma. Front. Oncol. 10, 309 (2020)

    Article  PubMed  PubMed Central  Google Scholar 

  19. W. Zhou, L. Chen, C. Li, R. Huang, M. Guo, S. Ning, J. Ji, X. Guo, G. Lou, X. Jia, J. Zhao, F. Luo, C. Li, Z. Qu, S. Yu, S. Tai, The multifaceted roles of long noncoding RNAs in pancreatic cancer: An update on what we know. Cancer. Cell. Int. 201(20), 1–11 (2020)

    Google Scholar 

  20. G. Ma, G. Li, W. Fan, Y. Xu, S. Song, K. Guo, Z. Liu, The role of long noncoding RNA AL161431.1 in the development and progression of pancreatic cancer. Front. Oncol. 11, 666313 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  21. M. Zhong, Z. Fang, B. Ruan, J. Xiong, J. Li, Z. Song, LINC01128 facilitates the progression of pancreatic cancer through up-regulation of LDHA by targeting MiR-561-5p. Cancer Cell Int. 22, 93 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. B. Zhang, C. Li, Z. Sun, Long non-coding RNA LINC00346, LINC00578, LINC00673, LINC00671, LINC00261, and SNHG9 are novel prognostic markers for pancreatic cancer. Am. J. Transl. Res. 10, 2648–2658 (2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  23. H. Zhang, M. Zhu, Y. Du, H. Zhang, Q. Zhang, Q. Liu, Z. Huang, L. Zhang, H. Li, L. Xu, X. Zhou, W. Zhu, Y. Shu, P. Liu, A panel of 12-LncRNA signature predicts survival of pancreatic adenocarcinoma. J. Cancer 10, 1550–1559 (2019)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. T.S. Barwal, U. Sharma, M.K. Rana, S. Bazala, I. Singh, M. Murmu, H.S. Kapoor, S. Thakur, M. Jain, A. Jain, A diagnostic and prognostic value of blood-based circulating long non-coding rnas in thyroid, pancreatic and ovarian cancer. Crit. Rev. Oncol. Hematol. 171, 103598 (2022)

    Article  PubMed  Google Scholar 

  25. G.G. Sharma, Y. Okada, D. Von Hoff, A. Goel, Non-coding RNA biomarkers in pancreatic ductal adenocarcinoma. Semin. Cancer Biol. 75, 153–168 (2020)

    Article  PubMed  CAS  Google Scholar 

  26. Y. Li, M.N. Al Hallak, P.A. Philip, A.S. Azmi, R.M. Mohammad, Non-coding rnas in pancreatic cancer diagnostics and therapy: Focus on LncRNAs, CircRNAs, and PiRNAs. Cancers (Basel) 13, 4161 (2021)

    Article  CAS  Google Scholar 

  27. M.N. Cabili, M.C. Dunagin, P.D. McClanahan, A. Biaesch, O. Padovan-Merhar, A. Regev, J.L. Rinn, A. Raj, Localization and abundance analysis of human LncRNAs at single-cell and single-molecule resolution. Genome Biol. 16, 20 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. S. Andrews. FastQC: A quality control tool for high throughput sequence data. (2019) [Internet] https://www.bioinformatics.babraham.ac.uk/projects/fastqc/

  29. A.M. Bolger, M. Lohse, B. Usadel, Trimmomatic: A flexible trimmer for illumina sequence data. Bioinformatics 30, 2114–2120 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. D. Kim, G. Pertea, C. Trapnell, H. Pimentel, R. Kelley, S.L. Salzberg, TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. M. Pertea, G.M. Pertea, C.M. Antonescu, T.-C. Chang, J.T. Mendell, S.L. Salzberg, StringTie enables improved reconstruction of a transcriptome from RNA-Seq reads. Nat. Biotechnol. 33, 290–295 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. C. Trapnell, B.A. Williams, G. Pertea, A. Mortazavi, G. Kwan, M.J. Van Baren, S.L. Salzberg, B.J. Wold, L. Pachter, Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511–515 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. C. Trapnell, A. Roberts, L. Goff, G. Pertea, D. Kim, D.R. Kelley, H. Pimentel, S.L. Salzberg, J.L. Rinn, L. Pachter, Differential gene and transcript expression analysis of RNA-Seq experiments with TopHat and Cufflinks. Nat. Protoc. 7, 562–578 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. M.K. Iyer, Y.S. Niknafs, R. Malik, U. Singhal, A. Sahu, Y. Hosono, T.R. Barrette, J.R. Prensner, J.R. Evans, S. Zhao, A. Poliakov, X. Cao, S.M. Dhanasekaran, Y.-M. Wu, D.R. Robinson, D.G. Beer, F.Y. Feng, H.K. Iyer, A.M. Chinnaiyan, The landscape of long noncoding RNAs in the human transcriptome. Nat. Genet. 47, 199–208 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Y. Zhao, H. Li, S. Fang, Y. Kang, W. Wu, Y. Hao, Z. Li, D. Bu, N. Sun, M.Q. Zhang, R. Chen, NONCODE 2016: An informative and valuable data source of long non-coding RNAs. Nucleic Acids Res. 44, D203 (2016)

    Article  CAS  PubMed  Google Scholar 

  36. B. Li, C.N. Dewey, RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12, 323 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. M.I. Love, W. Huber, S. Anders, Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2. Genome Biol. 15, 550 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. H. Wickham, ggplot2: elegant graphics for data analysis. (Springer-Verlag, New York, 2016)

  39. A.R. Quinlan, I.M. Hall, BEDTools: A flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. L. Kong, Y. Zhang, Z.-Q. Ye, X.-Q. Liu, S.-Q. Zhao, L. Wei, G. Gao, CPC: Assess the protein-coding potential of transcripts using sequence features and support vector machine. Nucleic Acids Res. 35, W345–W349 (2007)

    Article  PubMed  PubMed Central  Google Scholar 

  41. M.F. Lin, I. Jungreis, M. Kellis, PhyloCSF: A comparative genomics method to distinguish protein coding and non-coding regions. Bioinformatics 27, i275–i282 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. B.J. Haas, A. Papanicolaou, M. Yassour, M. Grabherr, P.D. Blood, J. Bowden, M.B. Couger, D. Eccles, B. Li, M. Lieber, M.D. MacManes, M. Ott, J. Orvis, N. Pochet, F. Strozzi, N. Weeks, R. Westerman, T. William, C.N. Dewey, R. Henschel, R.D. LeDuc, N. Friedman, A. Regev, De Novo transcript sequence reconstruction from RNA-Seq using the trinity platform for reference generation and analysis. Nat. Protoc. 8, 1494–1512 (2013)

    Article  CAS  PubMed  Google Scholar 

  43. S.F. Altschul, W. Gish, W. Miller, E.W. Myers, D.J. Lipman, Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990)

    Article  CAS  PubMed  Google Scholar 

  44. P. Langfelder, S. Horvath, WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics 9, 559 (2008)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. J. Reimand, T. Arak, P. Adler, L. Kolberg, S. Reisberg, H. Peterson, J. Vilo, G:Profiler-a web server for functional interpretation of gene lists (2016 Update). Nucleic Acids Res. 44, W83–W89 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gene Ontology Consortium, The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 32, 258D – 261 (2004)

    Article  CAS  Google Scholar 

  47. M. Kanehisa, Y. Sato, M. Kawashima, M. Furumichi, M. Tanabe, KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44, D457–D462 (2016)

    Article  CAS  PubMed  Google Scholar 

  48. A. Fabregat, S. Jupe, L. Matthews, K. Sidiropoulos, M. Gillespie, P. Garapati, R. Haw, B. Jassal, F. Korninger, B. May, M. Milacic, C.D. Roca, K. Rothfels, C. Sevilla, V. Shamovsky, S. Shorser, T. Varusai, G. Viteri, J. Weiser, G. Wu, L. Stein, H. Hermjakob, P. D’Eustachio, The reactome pathway knowledgebase. Nucleic Acids Res. 46, D649–D655 (2018)

    Article  CAS  PubMed  Google Scholar 

  49. J. Peng, B.F. Sun, C.Y. Chen, J.Y. Zhou, Y.S. Chen, H. Chen, L. Liu, D. Huang, J. Jiang, G.S. Cui, Y.Y.G.Y. Yang, W. Wang, D. Guo, M. Dai, J. Guo, T. Zhang, Q. Liao, Y. Liu, Y.Y.L.Y. Zhao, D.L. Han, Y.Y.L.Y. Zhao, Y.Y.G.Y. Yang, W. Wu, Single-cell RNA-Seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. Cell Res. 29, 725–738 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. T.D. Schmittgen, K.J. Livak, Analyzing real-time PCR data by the comparative C(T) method. Nat. Protoc. 3, 1101–1108 (2008)

    Article  CAS  PubMed  Google Scholar 

  51. R. Kleinhans, M. Woywod, M. Schmidbauer, W. Wirths, E. Kottkamp (2019) [internet]. https://www.ols-bio.de/products/incubator-microscope-zencell-owl

  52. C.A. Schneider, W.S. Rasband, K.W. Eliceiri, NIH image to ImageJ: 25 Years of image analysis. Nat. Methods 9, 671–675 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. C. Klijn, S. Durinck, E.W. Stawiski, P.M. Haverty, Z. Jiang, H. Liu, J. Degenhardt, O. Mayba, F. Gnad, J. Liu, G. Pau, J. Reeder, Y. Cao, K. Mukhyala, S.K. Selvaraj, M. Yu, G.J. Zynda, M.J. Brauer, T.D. Wu, R.C. Gentleman, G. Manning, R.L. Yauch, R. Bourgon, D. Stokoe, Z. Modrusan, R.M. Neve, F.J. de Sauvage, J. Settleman, S. Seshagiri, Z. Zhang, A comprehensive transcriptional portrait of human cancer cell lines. Nat. Biotechnol. 33, 306–312 (2015)

    Article  CAS  PubMed  Google Scholar 

  54. M. Guttman, J.L. Rinn, Modular regulatory principles of large non-coding RNAs. Nature 482, 339–346 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. L. Wan, J. Han, T. Liu, S. Dong, F. Xie, H. Chen, J. Huang, Scaffolding protein SPIDR/KIAA0146 connects the bloom syndrome helicase with homologous recombination repair. Proc. Natl. Acad. Sci. U. S. A. 110, 10646–10651 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. M.T. Villoria, P. Gutiérrez-Escribano, E. Alonso-Rodríguez, F. Ramos, E. Merino, A. Campos, A. Montoya, H. Kramer, L. Aragón, A. Clemente-Blanco, PP4 phosphatase cooperates in recombinational DNA repair by enhancing double-strand break end resection. Nucleic Acids Res. 47, 10706–10727 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. W.F. Doolittle, We simply cannot go on being so vague about “Function.” Genome Biol. 19, 223 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  58. R.W. Yao, Y. Wang, L.L. Chen, Cellular functions of long noncoding RNAs. Nat. Cell Biol. 21, 542–551 (2019)

    Article  CAS  PubMed  Google Scholar 

  59. D.J. Hanly, M. Esteller, M. Berdasco, Interplay between long non-coding RNAs and epigenetic machinery: Emerging targets in cancer?. Philos. Trans. R. Soc. B Biol. Sci. 373, 20170074 (2018)

    Article  CAS  Google Scholar 

  60. N. Waddell, M. Pajic, A.M. Patch, D.K. Chang, K.S. Kassahn, P. Bailey, A.L. Johns, D. Miller, K. Nones, K. Quek, M.C.J. Quinn, A.J. Robertson, M.Z.H. Fadlullah, T.J.C. Bruxner, A.N. Christ, I. Harliwong, S. Idrisoglu, S. Manning, C. Nourse, E. Nourbakhsh, S. Wani, P.J. Wilson, E. Markham, N. Cloonan, M.J. Anderson, J.L. Fink, O. Holmes, S.H. Kazakoff, C. Leonard, F. Newell, B. Poudel, S. Song, D. Taylor, N. Waddell, S. Wood, Q. Xu, J. Wu, M. Pinese, M.J. Cowley, H.C. Lee, M.D. Jones, A.M. Nagrial, J. Humphris, L.A. Chantrill, V. Chin, A.M. Steinmann, A. Mawson, E.S. Humphrey, E.K. Colvin, A. Chou, C.J. Scarlett, A.V. Pinho, M. Giry-Laterriere, I. Rooman, J.S. Samra, J.G. Kench, J.A. Pettitt, N.D. Merrett, C. Toon, K. Epari, N.Q. Nguyen, A. Barbour, N. Zeps, N.B. Jamieson, J.S. Graham, S.P. Niclou, R. Bjerkvig, R. Grützmann, D. Aust, R.H. Hruban, A. Maitra, C.A. Iacobuzio-Donahue, C.L. Wolfgang, R.A. Morgan, R.T. Lawlor, V. Corbo, C. Bassi, M. Falconi, G. Zamboni, G. Tortora, M.A. Tempero, A.J. Gill, J.R. Eshleman, C. Pilarsky, A. Scarpa, E.A. Musgrove, J.V. Pearson, A.V. Biankin, S.M. Grimmond, Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 518, 495–501 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. D.S. Sutaria, J. Jiang, A.C.P. Azevedo-Pouly, E.J. Lee, M.R. Lerner, D.J. Brackett, J. Vandesompele, P. Mestdagh, T.D. Schmittgen, Expression profiling identifies the noncoding processed transcript of HNRNPU with proliferative properties in pancreatic ductal adenocarcinoma. Non-coding RNA 3, 24 (2017)

    Article  PubMed Central  CAS  Google Scholar 

  62. Y. Lian, J. Yang, Y. Lian, C. Xiao, X. Hu, H. Xu, DUXAP8, a pseudogene derived LncRNA, promotes growth of pancreatic carcinoma cells by epigenetically silencing CDKN1A and KLF2. Cancer Commun. 38, 64 (2018)

    Article  Google Scholar 

  63. L. Statello, C.J. Guo, L.L. Chen, M. Huarte, Gene regulation by long non-coding RNAs and its biological functions. Nat. Rev. Mol. Cell Biol. 22, 96–118 (2020)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. T.K. Kim, M. Hemberg, J.M. Gray, Enhancer RNAs: A class of long noncoding RNAs synthesized at enhancers. Cold Spring Harb. Perspect. Biol. 7, a018622 (2015)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. E. Grossi, I. Raimondi, E. Goñi, J. González, F.P. Marchese, V. Chapaprieta, J.I. Martín-Subero, S. Guo, M. Huarte, A LncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions. Nat. Commun. 11, 936 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. C.A. Melo, J. Drost, P.J. Wijchers, H. van de Werken, E. de Wit, J.A.F.O. Vrielink, R. Elkon, S.A. Melo, N. Léveillé, R. Kalluri, W. de Laat, R. Agami, ERNAs are required for P53-dependent enhancer activity and gene transcription. Mol. Cell 49, 524–535 (2013)

    Article  CAS  PubMed  Google Scholar 

  67. Z. Zhang, J.H. Lee, H. Ruan, Y. Ye, J. Krakowiak, Q. Hu, Y. Xiang, J. Gong, B. Zhou, L. Wang, C. Lin, L. Diao, G.B. Mills, W. Li, L. Han, Transcriptional landscape and clinical utility of enhancer RNAs for ERNA-targeted therapy in cancer. Nat. Commun. 10, 4562 (2019)

    CAS  Google Scholar 

  68. J. Xing, H. Liu, W. Jiang, L. Wang, LncRNA-Encoded peptide: Functions and predicting methods. Front. Oncol. 10, 622294 (2021)

    Article  PubMed  PubMed Central  Google Scholar 

  69. M. Ye, J. Zhang, M. Wei, B. Liu, K. Dong, Emerging role of long noncoding RNA-encoded micropeptides in cancer. Cancer Cell Int. 20, 506 (2020)

    Article  CAS  Google Scholar 

  70. A.C. Tahira, M.S. Kubrusly, M.F. Faria, B. Dazzani, R.S. Fonseca, V. Maracaja-Coutinho, S. Verjovski-Almeida, M.C.C. Machado, E.M. Reis, Long noncoding Intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer. Mol. Cancer 10, 141 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. X.L. Fu, D.J. Liu, T.T. Yan, J.Y. Yang, M.W. Yang, J. Li, Y.M. Huo, W. Liu, J.F. Zhang, J. Hong, R. Hua, H.Y. Chen, Y.W. Sun, Analysis of long non-coding RNA expression profiles in pancreatic ductal adenocarcinoma. Sci. Rep. 6, 33535 (2016)

    CAS  Google Scholar 

  72. M. Zhang, Y. Zhao, Y. Zhang, D. Wang, S. Gu, W. Feng, W. Peng, A. Gong, M. Xu, LncRNA UCA1 promotes migration and invasion in pancreatic cancer cells via the Hippo pathway. Biochim. Biophys. Acta - Mol. Basis Dis. 1864, 1770–1782 (2018)

    Article  CAS  PubMed  Google Scholar 

  73. J. Wang, Z. He, J. Xu, P. Chen, J. Jiang, Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding MiR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling. Cell Death Dis. 12, 36 (2021)

    CAS  Google Scholar 

  74. Z. Deng, X. Li, Y. Shi, Y. Lu, W. Yao, J. Wang, A novel autophagy-related IncRNAs signature for prognostic prediction and clinical value in patients with pancreatic cancer. Front. Cell Dev. Biol. 8, 1504 (2020)

    Article  Google Scholar 

  75. T. Yu, G. Li, C. Wang, G. Gong, L. Wang, C. Li, Y. Chen, X. Wang, MIR210HG regulates glycolysis, cell proliferation, and metastasis of pancreatic cancer cells through MiR-125b-5p/HK2/PKM2 Axis. RNA Biol. 18, 2513–2530 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. D.D. Li, Z.Q. Fu, Q. Lin, Y. Zhou, Q.B. Zhou, Z.H. Li, L.P. Tan, R.F. Chen, Y.M. Liu, Linc00675 is a novel marker of short survival and recurrence in patients with pancreatic ductal adenocarcinoma. World J. Gastroenterol. 21, 9348–9357 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Y. Huang, A. Ling, S. Pareek, R.S. Huang, Oncogene or tumor suppressor? Long noncoding rnas role in patient’s prognosis varies depending on disease type. Transl. Res. 230, 98–110 (2021)

    Article  CAS  PubMed  Google Scholar 

  78. X. Zhao, P. Wang, J. Liu, J. Zheng, Y. Liu, J. Chen, Y. Xue, Gas5 exerts tumor-suppressive functions in human glioma cells by targeting MiR-222. Mol. Ther. 23, 1899–1911 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. X. Wen, X. Tang, Y. Li, X. Ren, Q. He, X. Yang, J. Zhang, Y. Wang, J. Ma, N. Liu, Microarray expression profiling of long non-coding RNAs involved in nasopharyngeal carcinoma metastasis. Int. J. Mol. Sci. 17, 1956 (2016)

    Article  PubMed Central  CAS  Google Scholar 

  80. Y. Sun, P. Peng, L. He, X. Gao, Identification of LncRNAs related to prognosis of patients with colorectal cancer. Technol. Cancer Res. Treat. 19, 1-6 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Q. Yu, X. Zhou, Q. Xia, J. Shen, J. Yan, J. Zhu, X. Li, M. Shu, Long non-coding RNA CCAT1 that can be activated by c-Myc promotes pancreatic cancer cell proliferation and migration. Am. J. Transl. Res. 8, 5444 (2016)

    CAS  PubMed  PubMed Central  Google Scholar 

  82. A.K. Angeles, D. Heckmann, N. Flosdorf, S. Duensing, H. Sültmann, The ERG-regulated LINC00920 promotes prostate cancer cell survival via the 14-3-3ε–FOXO pathway. Mol. Cancer Res. 18, 1545–1559 (2020)

    Article  CAS  PubMed  Google Scholar 

  83. Y. Wang, J.-H. Lu, Q.-N. Wu, Y. Jin, D.-S. Wang, Y.-X. Chen, J. Liu, X.-J. Luo, Q. Meng, H.-Y. Pu, Y.-N. Wang, P.-S. Hu, Z.-X. Liu, Z.-L. Zeng, Q. Zhao, R. Deng, X.-F. Zhu, H.-Q. Ju, R.-H. Xu, LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer. Mol. Cancer 18, 174 (2019)

    Google Scholar 

  84. Y. Kawasaki, M. Miyamoto, T. Oda, K. Matsumura, L. Negishi, R. Nakato, S. Suda, N. Yokota, K. Shirahige, T. Akiyama, The novel LncRNA CALIC upregulates AXL to promote colon cancer metastasis. EMBO Rep. 20, e47052 (2019)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. J.-B.M. Koorstra, C.A. Karikari, G. Feldmann, S. Bisht, P.L. Rojas, G.J.A. Offerhaus, H. Alvarez, A. Maitra, The Axl receptor tyrosine kinase confers an adverse prognostic influence in pancreatic cancer and represents a new therapeutic target. Cancer Biol. Ther. 8, 618 (2009)

    Article  CAS  PubMed  Google Scholar 

  86. Y.-C. Weng, J. Ma, J. Zhang, J.-C. Wang, Long non-coding RNA LINC01133 silencing exerts antioncogenic effect in pancreatic cancer through the methylation of DKK1 promoter and the activation of Wnt signaling pathway. Cancer Biol. Ther. 20, 368 (2019)

    Article  CAS  PubMed  Google Scholar 

  87. Y. Liu, T. Tang, X. Yang, P. Qin, P. Wang, H. Zhang, M. Bai, R. Wu, F. Li, Tumor-derived exosomal long noncoding RNA LINC01133, regulated by periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-Catenin pathway by silencing AXIN2. Oncogene 4017(40), 3164–3179 (2021)

    Article  CAS  Google Scholar 

  88. S. Ghafouri-Fard, M. Taheri, UCA1 long non-coding RNA: An update on its roles in malignant behavior of cancers. Biomed. Pharmacother. 120, 109459 (2019)

    Article  CAS  PubMed  Google Scholar 

  89. Y. Zhou, Y. Chen, W. Ding, Z. Hua, L. Wang, Y. Zhu, H. Qian, T. Dai, LncRNA UCA1 impacts cell proliferation, invasion, and migration of pancreatic cancer through regulating MiR-96/FOXO3. IUBMB Life 70, 276–290 (2018)

    Article  CAS  PubMed  Google Scholar 

  90. P. Chen, D. Wan, D. Zheng, Q. Zheng, F. Wu, Q. Zhi, Long non-coding RNA UCA1 promotes the tumorigenesis in pancreatic cancer. Biomed. Pharmacother. 83, 1220–1226 (2016)

    Article  CAS  PubMed  Google Scholar 

  91. Q. Liao, C. Liu, X. Yuan, S. Kang, R. Miao, H. Xiao, G. Zhao, H. Luo, D. Bu, H. Zhao, G. Skogerbø, Z. Wu, Y. Zhao, Large-scale prediction of long non-coding RNA functions in a coding–non-coding gene co-expression network. Nucleic Acids Res. 39, 3864–3878 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. M. Guttman, I. Amit, M. Garber, C. French, M.F. Lin, D. Feldser, M. Huarte, O. Zuk, B.W. Carey, J.P. Cassady, M.N. Cabili, R. Jaenisch, T.S. Mikkelsen, T. Jacks, N. Hacohen, B.E. Bernstein, M. Kellis, A. Regev, J.L. Rinn, E.S. Lander, Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458, 223–227 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. X. Guo, L. Gao, Q. Liao, H. Xiao, X. Ma, X. Yang, H. Luo, G. Zhao, D. Bu, F. Jiao, Q. Shao, R. Chen, Y. Zhao, Long non-coding RNAs function annotation: A global prediction method based on Bi-Colored networks. Nucleic Acids Res. 41, e35 (2013)

    Article  CAS  PubMed  Google Scholar 

  94. M. Giulietti, A. Righetti, G. Principato, F. Piva, LncRNA Co-expression network analysis reveals novel biomarkers for pancreatic cancer. Carcinogenesis 39, 1016–1025 (2018)

    Article  CAS  PubMed  Google Scholar 

  95. S.S. Pinho, C.A. Reis, Glycosylation in cancer: Mechanisms and clinical implications. Nat. Rev. Cancer 159(15), 540–555 (2015)

    Article  CAS  Google Scholar 

  96. H. Suh, K. Pillai, D.L. Morris, Mucins in pancreatic cancer: Biological role, implications in carcinogenesis and applications in diagnosis and therapy. Am. J. Cancer Res. 7, 1372 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  97. L.A. Mathews, S.M. Cabarcas, E.M. Hurt, X. Zhang, E.M. Jaffee, W.L. Farrar, Increased expression of DNA repair genes in invasive human pancreatic cancer cells. Pancreas 40, 730 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. A.A. Connor, R.E. Denroche, G.H. Jang, M. Lemire, A. Zhang, M. Chan-Seng-Yue, G. Wilson, R.C. Grant, D. Merico, I. Lungu, J.M.S. Bartlett, D. Chadwick, S. Ben Liang, J. Eagles, F. Mbabaali, J.K. Miller, P. Krzyzanowski, H. Armstrong, X. Luo, L.G.T. Jorgensen, J.M. Romero, P. Bavi, S.E. Fischer, S. Serra, S. Hafezi-Bakhtiari, D. Caglar, M.H.A. Roehrl, S. Cleary, M.A. Hollingsworth, G.M. Petersen, S. Thayer, C.H.L. Law, S. Nanji, T. Golan, A.L. Smith, A. Borgida, A. Dodd, D. Hedley, B.G. Wouters, G.M. O’Kane, J.M. Wilson, G. Zogopoulos, F. Notta, J.J. Knox, S. Gallinger, Integration of genomic and transcriptional features in pancreatic cancer reveals increased cell cycle progression in metastases. Cancer. Cell. 35, 267-282.e7 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. M.R. Makena, H. Gatla, D. Verlekar, S. Sukhavasi, M.K. Pandey, K.C. Pramanik, Wnt/β-Catenin signaling: The Culprit in pancreatic carcinogenesis and therapeutic resistance. Int. J. Mol. Sci. 20, 4242 (2019)

    Article  CAS  Google Scholar 

  100. S. Eser, A. Schnieke, G. Schneider, D. Saur, Oncogenic KRAS signalling in pancreatic cancer. Br. J. Cancer 111, 817–822 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. G. Mantini, A.M. Vallés, T.Y.S. Le Large, M. Capula, N. Funel, T.V. Pham, S.R. Piersma, G. Kazemier, M.F. Bijlsma, E. Giovannetti, C.R. Jimenez, Co-Expression analysis of pancreatic cancer proteome reveals biology and prognostic biomarkers. Cell. Oncol. 43, 1147–1159 (2020)

    Article  CAS  Google Scholar 

  102. P.T.W. Cohen, A. Philp, C. Vázquez-Martin, Protein phosphatase 4 – from obscurity to vital functions. FEBS Lett. 579, 3278–3286 (2005)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Júlio César Gomes de Sousa Filho (In Memorian) for technical support in the siRNA-mediated knockdown experiments.

Funding

The study was funded by a research grant from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) to EMR (grant nº 2013/13844–2) and DSB (grant nº 2016/19757–2). OJS, TB, LBCAM received fellowships from FAPESP. VFP, DVSP, ERB received fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). DOP received a fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). EMR and DSB are recipients of established researcher fellowships from CNPq.

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Author notes

  1. Vinicius Ferreira da Paixão and Omar Julio Sosa contributed equally.

Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, Cidade Universitária, São Paulo, SP, 05508-900, Brazil

    Vinicius Ferreira da Paixão, Bianca Dazzani, Thalita Bueno Corrêa, Luís Bruno da Cruz e Alves-de-Moraes, Diogo de Oliveira Pessoa, Victoria de Paiva Oliveira, Ricardo Alberto Chiong Zevallos, Lilian Cristina Russo, Fabio Luis Forti, João Carlos Setubal, Daniela Sanchez Bassères & Eduardo Moraes Reis

  2. Programa Interunidades de Pós-Graduação em Bioinformática, Universidade de São Paulo, São Paulo, SP, Brazil

    Omar Julio Sosa, Diogo Vieira da Silva Pellegrina & Ester Risério Bertoldi

  3. Departamento de Ciência da Computação, Instituto de Matemática e Estatística, Universidade de São Paulo, São Paulo, SP, Brazil

    João Eduardo Ferreira

  4. Departamento de Oncologia Médica, AC Camargo Cancer Center, São Paulo, SP, Brazil

    Helano Carioca Freitas

  5. Departamento de Gastroenterologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil

    José Jukemura

  6. Departamento de Emergências Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil

    Marcel Cerqueira César Machado

  7. Departamento de Anatomia Patológica - AC Camargo Cancer Center, São Paulo, SP, Brazil

    Maria Dirlei Begnami

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  1. Vinicius Ferreira da Paixão
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Contributions

Conceived and designed the experiments: VFP, OJS, DVSP, DSB, EMR. Performed the experiments: VFP, OJS, DVSP. BD, TBC, ERB, DOP, VPO, RACZ, LCR. Analyzed the data: VFP, OJS, DVSP, BD, TBC, ERB, DOP, VPO, RACZ, LCRV, FLF, HCF, DSB, EMR. Contributed reagents/materials/analysis tools: LBCAM, JJ, MCCM, JEF, JCS, MDB. Wrote the manuscript: VFP, OJS, EMR. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Eduardo Moraes Reis.

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Ethics approval and consent to participate

Clinical samples used in this study were retrieved from the A.C. Camargo Cancer Center biorepository with informed consent. The study was approved by the Ethics Committee of the Institution (nº: 1839/13) and the study is registered at the research regulatory platform of the Brazilian Ministry of Health (CAAE: 15059213.0.0000.5432). The collection of human PDAC specimens for PDX generation was carried out with patient informed consent and approval of the Institutional Review Board of Ethics in Research from collaborating institutions (Hospital Sírio-Libanês, Hospital Alemão Oswaldo Cruz and Hospital 9 de Julho, Sao Paulo, Brazil) and the study is registered at the research regulatory platform of the Brazilian Ministry of Health (CAAE: 36005314.1.0000.5461).

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da Paixão, V.F., Sosa, O.J., da Silva Pellegrina, D.V. et al. Annotation and functional characterization of long noncoding RNAs deregulated in pancreatic adenocarcinoma. Cell Oncol. 45, 479–504 (2022). https://doi.org/10.1007/s13402-022-00678-5

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