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Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways

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Tumor Biology

Abstract

Competing endogenous RNAs (ceRNAs) are RNA transcripts which can communicate with each other by decreasing targeting concentration of micro-RNA (miRNA) with the derepression of other messenger RNAs (mRNAs) having the common miRNA response elements (MREs). Oncocers are ceRNAs taking crucial roles in oncogenic pathways processed in many types of cancer, and this study analyzes oncocer-mediated cross-talk by sponging microRNAs (miRNAs) in these pathways. While doing this, breast, liver, colon, prostate, gastric, lung, endometrium, thyroid and epithelial cancers and melanoma, rhabdomyosarcoma, glioblastoma, acute promyelocytic leukemia, retinoblastoma, and neuroblastoma were analyzed with respect to ceRNA-based carcinogenesis. This study defines, firstly, oncocers in the literature and contains all oncocer-related findings found up to now. Therefore, it will help to increase our comprehension about oncocer-mediated mechanisms. Via this study, a novel perspective would be produced to make clear cancer mechanisms and suggest novel approaches to regulate ceRNA networks via miRNA competition for cancer therapeutics.

Multiple RNA transcripts have common MREs for the similar miRNA in their 3′-untranslated regions (3′-UTRs). Upregulation of ceRNAs rises the abundance of specific MREs and shifts the miRNA pool distribution, as a result, leading to the increased expression of target mRNA. The depot of genomic mutations and epigenetic alterations changing gene function and expression causes cancers. Herewith, genome-based somatic base-pair mutations, DNA copy number alterations, chromosomal translocation, also transcript fusions, alternative splicing are usually seen in cancer situations. Consequently, such cases causing changed UTR expression in transcripts influence the levels of MRE or present new MREs into the cells. Alterations in MREs of ceRNAs affect the capability of a specific mRNA transcript to attach or titrate miRNAs. As a result, the disturbed ceRNA network can lead to diseases and cancers. As a new term in RNA world, oncocers—the name for ceRNAs taking crucial roles in oncogenic pathways—are processed in many types of cancer, and oncocer-mediated cross-talk are analyzed by sponging miRNAs in these pathways.

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Abbreviations

3′-UTR:

3′-Untranslated region

ARM:

Alveolar rhabdomyosarcoma

ATXN3:

Ataxin 3

ceRNA:

Competing endogenous RNA

ceRNET:

ceRNA network

EMT:

Epithelial-to-mesenchymal transition

ERM:

Embryonic rhabdomyosarcoma

ET:

Endometrial tumorspheres

FGFR4:

Fibroblast growth factor receptor 4

HDACi:

Histone deacetylase inhibitors

HULC:

Highly upregulated in liver cancer

IGFR1:

Insulin like growth factor 1 receptor

lncRNA:

Long noncoding RNAs

miRNA:

Micro RNA

MRE:

MiRNA response element

ncRNA:

Noncoding RNA

PTCSC3:

Papillary thyroid carcinoma susceptibility candidate 3

ZEB:

Zinc finger E-box-binding homeobox

References

  1. Kataoka M, Wang D-Z. Non-coding RNAs including miRNAs and lncRNAs in cardiovascular biology and disease. Cells. 2014;3:883–98.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kameswaran V, Kaestner KH. The missing lnc (RNA) between the pancreatic β-cell and diabetes. Front Genet. 2014;5:200.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.

    Article  CAS  PubMed  Google Scholar 

  5. Tan J, Marques A. The miRNA-mediated cross-talk between transcripts provides a novel layer of posttranscriptional regulation. Adv Genet. 2013;85:149–99.

    Google Scholar 

  6. Ergun S, Arman K, Temiz E, Bozgeyik İ, Yumrutaş Ö, et al. Expression patterns of miR-221 and its target caspase-3 in different cancer cell lines. Mol Biol Rep. 2014;41:5877–81.

    Article  CAS  PubMed  Google Scholar 

  7. Arman K, Ergün S, Temiz E, Öztuzcu S. The interrelationship between HER2 and CASP3/8 with apoptosis in different cancer cell lines. Mol Biol Rep. 2014;41(12):1–6.

    Article  Google Scholar 

  8. Ergün S, Ulasli M, Igci Y, Igci M, Kırkbes S, et al. The association of the expression of miR-122-5p and its target ADAM10 with human breast cancer. Mol Biol Rep. 2015;42:497–505.

    Article  PubMed  Google Scholar 

  9. Costa V, Esposito R, Aprile M, Ciccodicola A. Non-coding RNA and pseudogenes in neurodegenerative diseases:“the (un) usual suspects”. Front Genet. 2012;3:231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ergün S, Öztuzcu S (2014) MiR-221: a critical player in apoptosis as a target of caspase-3. Cancer Cell Microenviron 1:10–14800/ccm. 14313.

  11. Sümbül AT, Göğebakan B, Ergün S, Yengil E, Batmacı CY, Yaldız M, Sezer A, Aldemir Ö, Özyılkan Ö. miR-204-5p expression in colorectal cancer: an autophagy-associated gene. Tumor Biol. 2014;35(12):12713–9.

  12. Ergun S, Oztuzcu S. Computational analysis of 3′ UTR Region of CASP3 with respect to miRSNPs and SNPs in targetting miRNAs. Comput Biol Chem. 2014;53PB:235–41.

    Article  PubMed  Google Scholar 

  13. Eades G, Zhang Y-S, Li Q-L, Xia J-X, Yao Y, et al. Long non-coding RNAs in stem cells and cancer. World J Clin Oncol. 2014;5:134.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rossi MN, Antonangeli F. LncRNAs: new players in apoptosis control. Int J Cell Biol. 2014;2014, 473857.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Serviss JT, Johnsson P, Grandér D. An emerging role for long non-coding RNAs in cancer metastasis. Front Genet. 2014;5:234.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Khvorova A, Wolfson A. New competition in RNA regulation. Nat Biotechnol. 2012;30:58–9.

    Article  CAS  PubMed  Google Scholar 

  17. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146:353–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ala U, Karreth FA, Bosia C, Pagnani A, Taulli R, et al. Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments. Proc Natl Acad Sci. 2013;110:7154–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kalyana-Sundaram S, Kumar-Sinha C, Shankar S, Robinson DR, Wu Y-M, et al. Expressed pseudogenes in the transcriptional landscape of human cancers. Cell. 2012;149:1622–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li L, Wang D, Xue M, Mi X, Liang Y, Wang P. 3′ UTR shortening identifies high-risk cancers with targeted dysregulation of the ceRNA network. Sci Rep. 2014;4:5406.

  21. Karreth FA, Pandolfi PP. ceRNA cross-talk in cancer: when ce-bling rivalries go awry. Cancer Discov. 2013;3:1113–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kartha RV, Subramanian S. Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation. Front Genet. 2014;5:8.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sarver AL, Subramanian S. Competing endogenous RNA database. Bioinformation. 2012;8:731.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Karreth FA, Ala U, Provero P, Pandolfi PP (2014) Pseudogenes as competitive endogenous RNAs: target prediction and validation. Pseudogenes. Springer. pp. 199–212.

  25. Cesana M, Daley GQ. Deciphering the rules of ceRNA networks. Proc Natl Acad Sci. 2013;110:7112–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yang J, Li T, Gao C, Lv X, Liu K, et al. FOXO1 3′ UTR functions as a ceRNA in repressing the metastases of breast cancer cells via regulating miRNA activity. FEBS Lett. 2014;588:3218–24.

    Article  CAS  PubMed  Google Scholar 

  27. Sen R, Ghosal S, Das S, Balti S, Chakrabarti J. Competing endogenous RNA: the key to posttranscriptional regulation. Sci World J. 2014;2014, 896206.

    Article  Google Scholar 

  28. Giza DE, Vasilescu C, Calin GA. MicroRNAs and ceRNAs: therapeutic implications of RNA networks. Expert Opin Biol Ther. 2014;14:1285–93.

    Article  CAS  PubMed  Google Scholar 

  29. Su X, Xing J, Wang Z, Chen L, Cui M, et al. microRNAs and ceRNAs: RNA networks in pathogenesis of cancer. Chin J Cancer Res. 2013;25:235.

    PubMed  PubMed Central  Google Scholar 

  30. Karreth FA, Tay Y, Perna D, Ala U, Tan SM, et al. In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell. 2011;147:382–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Berger MF, Levin JZ, Vijayendran K, Sivachenko A, Adiconis X, et al. Integrative analysis of the melanoma transcriptome. Genome Res. 2010;20:413–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tay Y, Kats L, Salmena L, Weiss D, Tan SM, et al. Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 2011;147:344–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sumazin P, Yang X, Chiu H-S, Chung W-J, Iyer A, et al. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell. 2011;147:370–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, et al. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011;147:358–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nie L, Wu H-J, Hsu J-M, Chang S-S, LaBaff AM, et al. Long non-coding RNAs: versatile master regulators of gene expression and crucial players in cancer. Am J Transl Res. 2012;4:127.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. de Giorgio A, Krell J, Harding V, Stebbing J, Castellano L. Emerging roles of competing endogenous RNAs in cancer: insights from the regulation of PTEN. Mol Cell Biol. 2013;33:3976–82.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Zhou X, Liu J, Wang W. Construction and investigation of breast-cancer-specific ceRNA network based on the mRNA and miRNA expression data. IET Syst Biol. 2014;8(3):96–103.

    Article  PubMed  Google Scholar 

  38. Ferracin M, Bassi C, Pedriali M, Pagotto S, D’Abundo L, et al. miR-125b targets erythropoietin and its receptor and their expression correlates with metastatic potential and ERBB2/HER2 expression. Mol Cancer. 2013;12:130.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Paci P, Colombo T, Farina L. Computational analysis identifies a sponge interaction network between long non-coding RNAs and messenger RNAs in human breast cancer. BMC Syst Biol. 2014;8:83.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Hou P, Zhao Y, Li Z, Yao R, Ma M, et al. LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis. Cell Death Dis. 2014;5:e1287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cha YH, Kim NH, Park C, Lee I, Kim HS, et al. MiRNA-34 intrinsically links p53 tumor suppressor and Wnt signaling. Cell Cycle. 2012;11:1273–81.

    Article  CAS  PubMed  Google Scholar 

  42. Fang L, Du WW, Yang X, Chen K, Ghanekar A, et al. Versican 3′-untranslated region (3′-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity. FASEB J. 2013;27:907–19.

    Article  CAS  PubMed  Google Scholar 

  43. Zhao L, Li F, Taylor EW. Can tobacco use promote HCV-induced miR-122 hijacking and hepatocarcinogenesis? Med Hypotheses. 2013;80:131–3.

    Article  CAS  PubMed  Google Scholar 

  44. Pilyugin M, Irminger-Finger I. Long non-coding RNA and microRNAs might act in regulating the expression of BARD1 mRNAs. Int J Biochem Cell Biol. 2014;54:356–67.

    Article  CAS  PubMed  Google Scholar 

  45. Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, et al. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010;465:1033–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Shen K, Mao R, Ma L, Li Y, Qiu Y, et al. Post‐transcriptional regulation of the tumor suppressor miR‐139‐5p and a network of miR‐139‐5p‐mediated mRNA interactions in colorectal cancer. FEBS J. 2014;281:3609–24.

    Article  CAS  PubMed  Google Scholar 

  47. Gao X, Fu C, Lao X, Tan Z. Competing endogenous RNA regulation mechanism and its role in the development and progression of colorectal cancer. Chin J Gastrointest Surg. 2012;15:1318–21.

    Google Scholar 

  48. Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014;505:344–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Liu X-h, Sun M, Nie F-q, Ge Y-b, Zhang E-b, et al. lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Xia T, Liao Q, Jiang X, Shao Y, Xiao B, et al. Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. Sci Rep. 2014;4:6088. doi:10.1038/srep06088.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Tay Y, Karreth FA, Pandolfi PP. Aberrant ceRNA activity drives lung cancer. Cell Res. 2014;24(3):259–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kumar MS, Armenteros-Monterroso E, East P, Chakravorty P, Matthews N, et al. HMGA2 functions as a competing endogenous RNA to promote lung cancer progression. Nature. 2014;505(7482):212–7.

    Article  CAS  PubMed  Google Scholar 

  53. Sacco J, Yau T, Darling S, Patel V, Liu H, et al. The deubiquitylase ataxin-3 restricts PTEN transcription in lung cancer cells. Oncogene. 2014;33(33):4265–72.

    Article  CAS  PubMed  Google Scholar 

  54. Zhou X, Gao Q, Wang J, Zhang X, Liu K, et al. Linc-RNA-RoR acts as a “sponge” against mediation of the differentiation of endometrial cancer stem cells by microRNA-145. Gynecol Oncol. 2014;133:333–9.

    Article  CAS  PubMed  Google Scholar 

  55. Kovalenko T, Sorokina A, Ozolinya L, Patrushev L. Methylation of the pseudogene PTENP1 5′-terminal region in endometrial cancer and hyperplasia. Russ J Bioorg Chem. 2013;39:397–405.

    Article  CAS  Google Scholar 

  56. Fan M, Li X, Jiang W, Huang Y, Li J, et al. A long non-coding RNA, PTCSC3, as a tumor suppressor and a target of miRNAs in thyroid cancer cells. Exp Ther Med. 2013;5:1143–6.

    PubMed  PubMed Central  Google Scholar 

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Ergun, S., Oztuzcu, S. Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways. Tumor Biol. 36, 3129–3136 (2015). https://doi.org/10.1007/s13277-015-3346-x

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