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In Vitro and In Vivo Comparative Analysis of Differentially Expressed Genes and Signaling Pathways in Breast Cancer Cells on Interaction with Mesenchymal Stem Cells

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Abstract

The interaction of breast cancer cells (BCC) with mesenchymal stem cells (MSC) plays a vital role in influencing the gene expression in breast cancer cells and thereby its uncontrolled proliferation, metastasis, and drug resistance. The extent of MSC governing the BCC or the extent of BCC influencing the MSC is a complex process, and the interaction strongly depends upon conditions such as the presence or absence of other cell types and in vivo tumor microenvironment or simple in vitro conditions. Hence, understanding this interaction through gene expression profiling may provide key insights about potential genes which can be targeted for breast cancer treatment. In the current study, in vitro microarray dataset and in vivo RNA-seq dataset of BCC on interaction with the MSC were downloaded from NCBI GEO database and analyzed for differentially expressed genes (DEGs), gene ontology (GO) term enrichment, and Reactome pathway analysis. To target the genes which have similar effect on both in vitro and in vivo, a comparative analysis was performed, 24 genes were commonly upregulated in both in vitro and in vivo datasets, while no common downregulated genes were observed. Out of which, 16 significant genes based upon fold change (logFC > 2) are identified for manipulating the interactions between MSC and BCC. Among them, 6 of the identified genes (FSTL1, LOX, SERPINE1, INHBA, FN1, and VEGFA) have already been reported to be upregulated in BCC on interaction with MSC by various studies. Further experiments need to be conducted to understand the role of remaining 10 identified genes (EFEMP1, IGFBP3, EDIL3, IFITM1, IGFBP4, ITGA5, SLC3A2, HRH1, PPP1R15A, and NNMT) in MSC-BCC interaction. In addition to the reported significant genes and its associated pathways, the expression of long non-coding RNA identified in this study may increase our understanding about the way MSC interacts with BCC and accelerate MSC-based treatment strategies for breast cancer.

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Data Availability

All data analyzed during this study are included in the following published articles (and its supplementary information files).

GSE171121 dataset: Tu, Z.,Schmoellerl, J.,Mariani, O.,Zheng, Y.,Hu, Y.,Vincent-Salomon, A.,& Karnoub, AE. (2021). The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer. NPJ breast cancer, 7,69.

GSE43306 dataset: Zhang, XH-F.,Jin, X.,Malladi, S.,Zou, Y.,Wen, YH.,Brogi, E.,Smid, M.,Foekens, JA.,& Massagué, J. (2013). Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell, 154,1060–1073.

References

  1. Malvia, S., Bagadi, S. A., Dubey, U. S., & Saxena, S. (2017). Epidemiology of breast cancer in Indian women. Asia-Pacific Journal of Clinical Oncology, 13, 289–295.

    Article  Google Scholar 

  2. Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D. M., Forman, D., & Bray, F. (2015). Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer, 136, E359–E386.

    Article  CAS  Google Scholar 

  3. Jayaraman, H., Ghone, N. V., Rajan, R. K., & Dashora, H. (2020). The role of cytokines in interactions of mesenchymal stem cells and breast cancer cells. Current Stem Cell Research & Therapy, 16, 443–453.

    Article  Google Scholar 

  4. Meleshina, A. V., Cherkasova, E. I., Shirmanova, M. V., Klementieva, N. V., Kiseleva, E. V., Snopova, L. B., Prodanets, N. N., & Zagaynova, E. V. (2015). Influence of mesenchymal stem cells on metastasis development in mice in vivo. Stem Cell Research and Therapy, 6, 1–10.

    Article  CAS  Google Scholar 

  5. Khakoo, A. Y., Pati, S., Anderson, S. A., Reid, W., Elshal, M. F., Rovira, I. I., Nguyen, A. T., Malide, D., Combs, C. A., Hall, G., Zhang, J., Raffeld, M., Rogers, T. B., Stetler-Stevenson, W., Frank, J. A., Reitz, M., & Finkel, T. (2006). Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. Journal of Experimental Medicine, 203, 1235–1247.

    Article  CAS  Google Scholar 

  6. Heerboth, S.,Housman, G.,Leary, M.,Longacre, M.,Byler, S.,Lapinska, K.,Willbanks, A.,& Sarkar, S. (2015). EMT and tumor metastasis. Clinical and Translational Medicine. 4(6), 1–13.

  7. Patel, S. A., Meyer, J. R., Greco, S. J., Corcoran, K. E., Bryan, M., & Rameshwar, P. (2010). Mesenchymal stem cells protect breast cancer cells through regulatory t cells: Role of mesenchymal stem cell-derived TGF-β. The Journal of Immunology, 184, 5885–5894.

    Article  CAS  Google Scholar 

  8. Razmkhah, M., Jaberipour, M., Erfani, N., Habibagahi, M., Talei, A Rasoul, & Ghaderi, A. (2011). Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-β1 and upregulate expression of regulatory molecules on T cells: Do they protect breast cancer cells from the immune response? Cellular Immunology, 266, 116–122.

    Article  CAS  Google Scholar 

  9. Chaturvedi, P., Gilkes, DM., Wong, CCL., Kshitiz., Luo, W.,Zhang, H., Wei, H., Takano, N., Schito, L., Levchenko, A., Semenza, GL. (2013). Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. Journal of Clinical Investigation, 123,189–205

  10. Martin, F. T., Dwyer, R. M., Kelly, J., Khan, S., Murphy, J. M., Curran, C., Miller, N., Hennessy, E., Dockery, P., Barry, F. P., O’Brien, T., & Kerin, M. J. (2010). Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: Stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Research and Treatment, 124, 317–326.

    Article  CAS  Google Scholar 

  11. McGuigan, A., Kelly, P., Turkington, R. C., Jones, C., Coleman, H. G., & McCain, R. S. (2018). Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World Journal of Gastroenterology, 24, 4846–4861.

    Article  Google Scholar 

  12. Tu, Z., Schmoellerl, J., Mariani, O., Zheng, Y., Hu, Y., Vincent-Salomon, A., & Karnoub, A. E. (2021). The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer. NPJ breast cancer, 7, 69.

    Article  CAS  Google Scholar 

  13. Zhang, X.H.-F., Jin, X., Malladi, S., Zou, Y., Wen, Y. H., Brogi, E., Smid, M., Foekens, J. A., & Massagué, J. (2013). Selection of bone metastasis seeds by mesenchymal signals in the primary tumor stroma. Cell, 154, 1060–1073.

    Article  CAS  Google Scholar 

  14. Carvalho, B. S., & Irizarry, R. A. (2010). A framework for oligonucleotide microarray preprocessing. Bioinformatics (Oxford, England), 26, 2363–2367.

    Article  CAS  Google Scholar 

  15. Chen, Y., Lun, A. T. L., & Smyth, G. K. (2016). From reads to genes to pathways: Differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline. F1000Research, 5, 1438.

    Google Scholar 

  16. McCarthy, D. J., Chen, Y., & Smyth, G. K. (2012). Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic acids research, 40, 4288–4297.

    Article  CAS  Google Scholar 

  17. Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010). edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 26, 139–140.

    Article  CAS  Google Scholar 

  18. Reimers, M., & Carey, V. J. (2006). Bioconductor: An open source framework for bioinformatics and computational biology. Methods in enzymology, 411, 119–134.

    Article  CAS  Google Scholar 

  19. Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research, 43, e47–e47.

    Article  Google Scholar 

  20. Liao, Y., Wang, J., Jaehnig, E. J., Shi, Z., & Zhang, B. (2019). WebGestalt 2019: Gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Research, 47, W199–W205.

    Article  CAS  Google Scholar 

  21. Durinck, S., Moreau, Y., Kasprzyk, A., Davis, S., De Moor, B., Brazma, A., & Huber, W. (2005). BioMart and Bioconductor: A powerful link between biological databases and microarray data analysis. Bioinformatics (Oxford, England), 21, 3439–3440.

    Article  CAS  Google Scholar 

  22. Hmadcha, A., Martin-Montalvo, A., Gauthier, B. R., Soria, B., & Capilla-Gonzalez, V. (2020). Therapeutic potential of mesenchymal stem cells for cancer therapy. Frontiers in bioengineering and biotechnology, 8, 43.

    Article  Google Scholar 

  23. Lenka, G., Shan, J., Halabi, N., Abuaqel, S. W. J., Goswami, N., Schmidt, F., Zaghlool, S., Romero, A. R., Subramanian, M., Boujassoum, S., Al-Bozom, I., Gehani, S., Khori, N. A., Bedognetti, D., Suhre, K., Ma, X., Dömling, A., Rafii, A., & Chouchane, L. (2020). STXBP6, reciprocally regulated with autophagy, reduces triple negative breast cancer aggressiveness. Clinical and Translational Medicine, 10, e147.

    Article  Google Scholar 

  24. Roselli, S., Pundavela, J., Demont, Y., Faulkner, S., Keene, S., Attia, J., Jiang, C. C., Zhang, X. D., Walker, M. M., & Hondermarck, H. (2015). Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion. Oncotarget, 6, 10473–10486.

    Article  Google Scholar 

  25. Chen, Z., Cao, Z., Zhang, W., Gu, M., Zhou, Z. D., Li, B., Li, J., Tan, E. K., & Zeng, L. (2017). LRRK2 interacts with ATM and regulates Mdm2–p53 cell proliferation axis in response to genotoxic stress. Human Molecular Genetics, 26, 4494–4505.

    Article  CAS  Google Scholar 

  26. Agalliu, I., San Luciano, M., Mirelman, A., Giladi, N., Waro, B., Aasly, J., Inzelberg, R., Hassin-Baer, S., Friedman, E., Ruiz-Martinez, J., Marti-Masso, J. F., Orr-Urtreger, A., Bressman, S., & Saunders-Pullman, R. (2015). Higher frequency of certain cancers in LRRK2 G2019S mutation carriers with Parkinson disease: A pooled analysis. JAMA Neurology, 72, 58–65.

    Article  Google Scholar 

  27. Qian, B. Z., Zhang, H., Li, J., He, T., Yeo, E. J., Soong, D. Y. H., Carragher, N. O., Munro, A., Chang, A., Bresnick, A. R., Lang, R. A., & Pollard, J. W. (2015). FLT1 signaling in metastasis-associated macrophages activates an inflammatory signature that promotes breast cancer metastasis. Journal of Experimental Medicine, 212, 1433–1448.

    Article  CAS  Google Scholar 

  28. Prijic, S., & Chang, J. T. (2022). ABCA1 expression is upregulated in an EMT in breast cancer cell lines via MYC-mediated de-repression of its proximal Ebox element. Biomedicines, 10, 581.

    Article  CAS  Google Scholar 

  29. Yao, G., Zhao, K., Bao, K., & Li, J. (2022). Radiation increases COL1A1, COL3A1, and COL1A2 expression in breast cancer. Open Medicine, 17, 329–340.

    Article  CAS  Google Scholar 

  30. Jander, R., Rauterberg, J., & Glanville, R. W. (1983). Further characterization of the three polypeptide chains of bovine and human short-chain collagen (intima collagen). European Journal of Biochemistry, 133, 39–46.

    Article  CAS  Google Scholar 

  31. Fang, X., Burg, M. A., Barritt, D., Dahlin-Huppe, K., Nishiyama, A., & Stallcup, W. B. (1999). Cytoskeletal reorganization induced by engagement of the NG2 proteoglycan leads to cell spreading and migration. Molecular biology of the cell, 10, 3373–3387.

    Article  CAS  Google Scholar 

  32. Bozoky, B., Savchenko, A., Guven, H., Ponten, F., Klein, G., & Szekely, L. (2014). Decreased decorin expression in the tumor microenvironment. Cancer Medicine, 3, 485.

    Article  CAS  Google Scholar 

  33. González-González, L., & Alonso, J. (2018). Periostin: A matricellular protein with multiple functions in cancer development and progression. Frontiers in Oncology, 8, 225.

    Article  Google Scholar 

  34. Sun, Y., Ho, G. H., Koong, H. N., Sivaramakrishnan, G., Ang, W. T., Koh, Q. M., & Lin, V. C. L. (2013). Down-regulation of Tripartite-motif containing 22 expression in breast cancer is associated with a lack of p53-mediated induction. Biochemical and Biophysical Research Communications, 441, 600–606.

    Article  CAS  Google Scholar 

  35. Zhang, Q., Lei, L., & Jing, D. (2020). Knockdown of SERPINE1 reverses resistance of triple-negative breast cancer to paclitaxel via suppression of VEGFA. Oncology Reports, 44, 1875.

    CAS  Google Scholar 

  36. Zhang, M., Gao, C. E., Li, W. H., Yang, Y., Chang, L., Dong, J., Ren, Y. X., & Chen, D. D. (2017). Microarray based analysis of gene regulation by mesenchymal stem cells in breast cancer. Oncology letters, 13, 2770–2776.

    Article  CAS  Google Scholar 

  37. Sakamoto, H., Koma, Y., Higashino, N., Kodama, T., Tanigawa, K., Shimizu, M., Fujikawa, M., Nishio, M., Shigeoka, M., Kakeji, Y., & Yokozaki, H. (2021). PAI-1 derived from cancer-associated fibroblasts in esophageal squamous cell carcinoma promotes the invasion of cancer cells and the migration of macrophages. Laboratory Investigation, 101, 353–368.

    Article  CAS  Google Scholar 

  38. Wang, T. H., Hsia, S. M., & Shieh, T. M. (2017). Lysyl oxidase and the tumor microenvironment. International Journal of Molecular Sciences, 18, 1–12.

    Article  Google Scholar 

  39. El-Haibi, C. P., Bell, G. W., Zhang, J., Collmann, A. Y., Wood, D., Scherber, C. M., Csizmadia, E., Mariani, O., Zhu, C., Campagne, A., Toner, M., Bhatia, S. N., Irimia, D., Vincent-Salomon, A., & Karnoub, A. E. (2012). Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy. Proceedings of the National Academy of Sciences of the United States of America, 109, 17460–17465.

    Article  CAS  Google Scholar 

  40. Burger, A. M., Leyland-Jones, B., Banerjee, K., Spyropoulos, D. D., & Seth, A. K. (2005). Essential roles of IGFBP-3 and IGFBP-rP1 in breast cancer. European journal of cancer (Oxford, England: 1990), 41, 1515–1527.

    Article  CAS  Google Scholar 

  41. Cheng, S., Huang, Y., Lou, C., He, Y., Zhang, Y., & Zhang, Q. (2019). FSTL1 enhances chemoresistance and maintains stemness in breast cancer cells via integrin β3/Wnt signaling under miR-137 regulation. Cancer biology & therapy, 20, 328–337.

    Article  CAS  Google Scholar 

  42. Kudo-Saito, C., Ishida, A., Shouya, Y., Teramoto, K., Igarashi, T., Kon, R., Saito, K., Awada, C., Ogiwara, Y., & Toyoura, M. (2018). Blocking the FSTL1-DIP2A axis improves anti-tumor immunity. Cell reports, 24, 1790–1801.

    Article  CAS  Google Scholar 

  43. Kudo-Saito, C., Fuwa, T., Murakami, K., & Kawakami, Y. (2013). Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction. Cancer Research, 73, 6185–6193.

    Article  CAS  Google Scholar 

  44. Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bächinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., & Sasaki, T. (2007). A comparative analysis of the fibulin protein family. Biochemical characterization, binding interactions, and tissue localization. The Journal of biological chemistry, 282, 11805–11816.

    Article  CAS  Google Scholar 

  45. Fico, F., & Santamaria-Martínez, A. (2020). The tumor microenvironment as a driving force of breast cancer stem cell plasticity. Cancers, 12, 3863.

    Article  CAS  Google Scholar 

  46. Hu, Y., Pioli, P. D., Siegel, E., Zhang, Q., Nelson, J., Chaturbedi, A., Mathews, M. S., Ro, D. I., Alkafeef, S., Hsu, N., Hamamura, M., Yu, L., Hess, K. R., Tromberg, B. J., Linskey, M. E., & Zhou, Y.-H. (2011). EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment. Molecular cancer, 10, 123.

    Article  CAS  Google Scholar 

  47. Kim, I. G., Kim, S. Y., Choi, S. I., Lee, J. H., Kim, K. C., & Cho, E. W. (2014). Fibulin-3-mediated inhibition of epithelial-to-mesenchymal transition and self-renewal of ALDH+ lung cancer stem cells through IGF1R signaling. Oncogene, 33, 3908–3917.

    Article  CAS  Google Scholar 

  48. Nomoto, S., Kanda, M., Okamura, Y., Nishikawa, Y., Qiyong, L., Fujii, T., Sugimoto, H., Takeda, S., & Nakao, A. (2010). Epidermal growth factor-containing fibulin-like extracellular matrix protein 1, EFEMP1, a novel tumor-suppressor gene detected in hepatocellular carcinoma using double combination array analysis. Annals of surgical oncology, 17, 923–932.

    Article  Google Scholar 

  49. Kirouac, D C., Saez-Rodriguez, J., Swantek, J., Burke, J. M., Lauffenburger, D. A., & Sorger, P. K. (2012). Creating and analyzing pathway and protein interaction compendia for modelling signal transduction networks. BMC Systems Biology, 6(29), 1–18.

  50. Kun, Z., Xin, G., Tao, W., Chenglong, Z., Dongsheng, W., Liang, T., Tielong, L., & Jianru, X. (2019). Tumor derived EDIL3 modulates the expansion and osteoclastogenesis of myeloid derived suppressor cells in murine breast cancer model. Journal of bone oncology, 16, 100238.

    Article  Google Scholar 

  51. Lee, J.-E., Moon, P.-G., Cho, Y.-E., Kim, Y.-B., Kim, I.-S., Park, H., & Baek, M.-C. (2016). Identification of EDIL3 on extracellular vesicles involved in breast cancer cell invasion. Journal of proteomics, 131, 17–28.

    Article  CAS  Google Scholar 

  52. Hamalian, S., Güth, R., Runa, F., Sanchez, F., Vickers, E., Agajanian, M., Molnar, J., Nguyen, T., Gamez, J., Humphries, J. D., Nayak, A., Humphries, M. J., Tchou, J., Zervantonakis, I. K., & Kelber, J. A. (2021). A SNAI2-PEAK1-INHBA stromal axis drives progression and lapatinib resistance in HER2-positive breast cancer by supporting subpopulations of tumor cells positive for antiapoptotic and stress signaling markers. Oncogene, 40, 5224–5235.

    Article  CAS  Google Scholar 

  53. Yu, Y., Wang, W., Lu, W., Chen, W., & Shang, A. (2021). Inhibin β-A (INHBA) induces epithelial-mesenchymal transition and accelerates the motility of breast cancer cells by activating the TGF-β signaling pathway. Bioengineered, 12, 4681–4696.

    Article  CAS  Google Scholar 

  54. Duss, S., Brinkhaus, H., Britschgi, A., Cabuy, E., Frey, D. M., Schaefer, D. J., & Bentires-Alj, M. (2014). Mesenchymal precursor cells maintain the differentiation and proliferation potentials of breast epithelial cells. Breast Cancer Research, 16, R60.

    Article  Google Scholar 

  55. Ogony, J., Choi, H. J., Lui, A., Cristofanilli, M., & Lewis-Wambi, J. (2016). Interferon-induced transmembrane protein 1 (IFITM1) overexpression enhances the aggressive phenotype of SUM149 inflammatory breast cancer cells in a signal transducer and activator of transcription 2 (STAT2)-dependent manner. Breast cancer research : BCR, 18, 25.

    Article  Google Scholar 

  56. Soikkeli, J., Podlasz, P., Yin, M., Nummela, P., Jahkola, T., Virolainen, S., Krogerus, L., Heikkilä, P., von Smitten, K., Saksela, O., & Hölttä, E. (2010). Metastatic outgrowth encompasses COL-I, FN1, and POSTN up-regulation and assembly to fibrillar networks regulating cell adhesion, migration, and growth. The American journal of pathology, 177, 387–403.

    Article  CAS  Google Scholar 

  57. Jun, B. H., Guo, T., Libring, S., Chanda, M. K., Paez, J. S., Shinde, A., Wendt, M. K., Vlachos, P. P., & Solorio, L. (2020). Fibronectin-expressing mesenchymal tumor cells promote breast cancer metastasis. Cancers, 12, 2553.

    Article  CAS  Google Scholar 

  58. Mita, K., Zhang, Z., Ando, Y., Toyama, T., Hamaguchi, M., Kobayashi, S., Hayashi, S., Fujii, Y., Iwase, H., & Yamashita, H. (2007). Prognostic significance of insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 expression in breast cancer. Japanese journal of clinical oncology, 37, 575–582.

    Article  Google Scholar 

  59. Severino, V., Alessio, N., Farina, A., Sandomenico, A., Cipollaro, M., Peluso, G., Galderisi, U., & Chambery, A. (2013). Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells. Cell death & disease, 4, e911.

    Article  CAS  Google Scholar 

  60. Fajka-Boja, R., Szebeni, G. J., Hunyadi-Gulyás, É., Puskás, L. G., & Katona, R. L. (2020). Polyploid adipose stem cells shift the balance of IGF1/IGFBP2 to promote the growth of breast cancer. Frontiers in Oncology, 10(157), 1–8.

  61. Pantano, F., Croset, M., Driouch, K., Bednarz-Knoll, N., Iuliani, M., Ribelli, G., Bonnelye, E., Wikman, H., Geraci, S., Bonin, F., Simonetti, S., Vincenzi, B., Hong, S. S., Sousa, S., Pantel, K., Tonini, G., Santini, D., & Clézardin, P. (2021). Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions. Oncogene, 40, 1284–1299.

    Article  CAS  Google Scholar 

  62. Cheuk, I.W.-Y., Siu, M. T., Ho, J.C.-W., Chen, J., Shin, V. Y., & Kwong, A. (2020). ITGAV targeting as a therapeutic approach for treatment of metastatic breast cancer. American journal of cancer research, 10, 211–223.

    CAS  Google Scholar 

  63. Ju, J. A., Godet, I., Ye, I. C., Byun, J., Jayatilaka, H., Lee, S. J., Xiang, L., Samanta, D., Lee, M. H., Wu, P.-H., Wirtz, D., Semenza, G. L., & Gilkes, D. M. (2017). Hypoxia selectively enhances integrin α(5)β(1) receptor expression in breast cancer to promote metastasis. Molecular cancer research : MCR, 15, 723–734.

    Article  CAS  Google Scholar 

  64. Chaturvedi, P., Gilkes, D. M., Takano, N., & Semenza, G. L. (2014). Hypoxia-inducible factor-dependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment. Proceedings of the National Academy of Sciences of the United States of America, 111, E2120–E2129.

    CAS  Google Scholar 

  65. Zhu, B., Cheng, D., Hou, L., Zhou, S., Ying, T., & Yang, Q. (2017). SLC3A2 is upregulated in human osteosarcoma and promotes tumor growth through the PI3K/Akt signaling pathway. Oncology reports, 37, 2575–2582.

    Article  CAS  Google Scholar 

  66. Furuya, M., Horiguchi, J., Nakajima, H., Kanai, Y., & Oyama, T. (2012). Correlation of L-type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis. Cancer science, 103, 382–389.

    Article  CAS  Google Scholar 

  67. El Ansari, R., Craze, M. L., Diez-Rodriguez, M., Nolan, C. C., Ellis, I. O., Rakha, E. A., & Green, A. R. (2018). The multifunctional solute carrier 3A2 (SLC3A2) confers a poor prognosis in the highly proliferative breast cancer subtypes. British journal of cancer, 118, 1115–1122.

    Article  Google Scholar 

  68. Fernández-Nogueira, P., Noguera-Castells, A., Fuster, G., Recalde-Percaz, L., Moragas, N., López-Plana, A., Enreig, E., Jauregui, P., Carbó, N., Almendro, V., Gascón, P., Bragado, P., & Mancino, M. (2018). Histamine receptor 1 inhibition enhances antitumor therapeutic responses through extracellular signal-regulated kinase (ERK) activation in breast cancer. Cancer letters, 424, 70–83.

    Article  Google Scholar 

  69. Song, P., Yang, S., Hua, H., Zhang, H., Kong, Q., Wang, J., Luo, T., & Jiang, Y. (2019). The regulatory protein GADD34 inhibits TRAIL-induced apoptosis via TRAF6/ERK-dependent stabilization of myeloid cell leukemia 1 in liver cancer cells. The Journal of biological chemistry, 294, 5945–5955.

    Article  CAS  Google Scholar 

  70. Liu, L., Ito, S., Nishio, N., Sun, Y., Tanaka, Y., & Isobe, K.-I. (2016). GADD34 promotes tumor growth by inducing myeloid-derived suppressor cells. Anticancer Research, 36, 4623–4628.

    Article  CAS  Google Scholar 

  71. Tsaytler, P., Harding, H. P., Ron, D., & Bertolotti, A. (2011). Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science (New York, NY), 332, 91–94.

    Article  CAS  Google Scholar 

  72. Sa-Nguanraksa, D., & O-Charoenrat, P. (2012). The role of vascular endothelial growth factor a polymorphisms in breast cancer. International Journal of Molecular Sciences, 13, 14845–14864.

    Article  CAS  Google Scholar 

  73. Zhu, W., Huang, L., Li, Y., Zhang, X., Gu, J., Yan, Y., Xu, X., Wang, M., Qian, H., & Xu, W. (2012). Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer letters, 315, 28–37.

    Article  CAS  Google Scholar 

  74. Wang, Y., Zeng, J., Wu, W., Xie, S., Yu, H., Li, G., Zhu, T., Li, F., Lu, J., Wang, G. Y., Xie, X., & Zhang, J. (2019). Nicotinamide N-methyltransferase enhances chemoresistance in breast cancer through SIRT1 protein stabilization. Breast cancer research : BCR, 21, 64.

    Article  Google Scholar 

  75. Seifert, R., Hoshino, J., & Kröger, H. (1984). Nicotinamide methylation. Tissue distribution, developmental and neoplastic changes. Biochimica et biophysica acta, 801, 259–264.

    Article  CAS  Google Scholar 

  76. Eckert, M. A., Coscia, F., Chryplewicz, A., Chang, J. W., Hernandez, K. M., Pan, S., Tienda, S. M., Nahotko, D. A., Li, G., Blaženović, I., Lastra, R. R., Curtis, M., Yamada, S. D., Perets, R., McGregor, S. M., Andrade, J., Fiehn, O., Moellering, R. E., Mann, M., & Lengyel, E. (2019). Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. Nature, 569, 723–728.

    Article  CAS  Google Scholar 

  77. Zhang, T., Hu, H., Yan, G., Wu, T., Liu, S., Chen, W., Ning, Y., & Lu, Z. (2019). Long non-coding RNA and breast cancer. Technology in cancer research & treatment, 18, 1–10.

    Article  Google Scholar 

  78. Wang, Z., Yang, B., Zhang, M., Guo, W., Wu, Z., Wang, Y., Jia, L., Li, S., Cancer, T., Atlas, G., & Xie, W. (2019). Cycle progression in cancer., 33, 706–720.

    Google Scholar 

  79. Yang, F., Shen, Y., Zhang, W., Jin, J., Huang, D., Fang, H., Ji, W., Shi, Y., Tang, L., Chen, W., Zhou, G., & Guan, X. (2018). An androgen receptor negatively induced long non-coding RNA ARNILA binding to miR-204 promotes the invasion and metastasis of triple-negative breast cancer. Cell Death and Differentiation, 25, 2209–2220.

    Article  CAS  Google Scholar 

  80. Karpov, D. S., Spirin, P. V., Zheltukhin, A. O., Tutyaeva, V. V., Zinovieva, O. L., Grineva, E. N., Matrosova, V. A., Krasnov, G. S., Snezhkina, A. V., Kudryavtseva, A. V., Prassolov, V. S., Mashkova, T. D., & Lisitsyn, N. A. (2020). Linc00973 induces proliferation arrest of drug-treated cancer cells by preventing P21 degradation. International Journal of Molecular Sciences, 21, 1–13.

    Article  Google Scholar 

  81. Yan, M., Zhang, L., Li, G., Xiao, S., Dai, J., & Cen, X. (2017). Long noncoding RNA linc-ITGB1 promotes cell migration and invasion in human breast cancer. Biotechnology and Applied Biochemistry, 64, 5–13.

    Article  CAS  Google Scholar 

  82. Wang, L., Luan, T., Zhou, S., Lin, J., Yang, Y., Liu, W., Tong, X., & Jiang, W. (2019). LncRNA HCP5 promotes triple negative breast cancer progression as a ceRNA to regulate BIRC3 by sponging miR-219a-5p. Cancer Medicine, 8, 4389–4403.

    Article  CAS  Google Scholar 

  83. Chen, G., Wang, K., Li, G., Wang, L., Xiao, Y., & Chen, B. (2020). Long noncoding RNA LAMTOR5-AS1 Interference affects microRNA-506-3p/E2F6-mediated behavior of non-small cell lung cancer cells. Oncology Research, 28, 945–959.

    Article  Google Scholar 

  84. Liu, B., Xiang, W., Liu, J., Tang, J., Wang, J., Liu, B., Long, Z., Wang, L., Yin, G., & Liu, J. (2021). The regulatory role of antisense lncRNAs in cancer. Cancer cell international, 21, 459.

    Article  CAS  Google Scholar 

  85. Xia, W., Liu, Y., Cheng, T., Xu, T., Dong, M., & Hu, X. (2020). Down-regulated lncRNA SBF2-AS1 inhibits tumorigenesis and progression of breast cancer by sponging microRNA-143 and repressing RRS1. Journal of Experimental and Clinical Cancer Research, 39, 1–16.

    Google Scholar 

  86. Wu, L., Xu, Q., Zhang, H., Li, M., Zhu, C., Jiang, M., Sang, X., Zhao, Y., Sun, Q., & Zhao, H. (2016). A new avenue for obtaining insight into the functional characteristics of long noncoding RNAs associated with estrogen receptor signaling. Scientific Reports, 6, 1–8.

    Google Scholar 

  87. Huang, J., Zhou, N., Watabe, K., Lu, Z., Wu, F., Xu, M., & Mo, Y.-Y. (2014). Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death & Disease, 5, e1008–e1008.

    Article  CAS  Google Scholar 

  88. Yang, Y., Yang, H., Xu, M., Zhang, H., Sun, M., Mu, P., Dong, T., Du, S., & Liu, K. (2018). Long non-coding RNA (lncRNA) MAGI2-AS3 inhibits breast cancer cell growth by targeting the Fas/FasL signalling pathway. Human Cell, 31, 232–241.

    Article  Google Scholar 

  89. Zhu, B., Finch-Edmondson, M., Leong, K. W., Zhang, X., Mitheera, V., Lin, Q. X. X., Lee, Y., Ng, W. T., Guo, H., Wan, Y., Sudol, M., & Dasgupta, R. (2021). LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer. Cell Death Discovery, 7, 369.

    Article  CAS  Google Scholar 

  90. Yue, G., Chen, C., Bai, L., Wang, G., Huang, Y., Wang, Y., Cui, H., & Xiao, Y. (2019). Knockdown of long noncoding RNA DLEU1 suppresses the progression of renal cell carcinoma by downregulating the Akt pathway. Molecular Medicine Reports, 20, 4551–4557.

    CAS  Google Scholar 

  91. Shin, V. Y., Chen, J., Cheuk, I.W.-Y., Siu, M.-T., Ho, C.-W., Wang, X., Jin, H., & Kwong, A. (2019). Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness. Cell Death & Disease, 10, 270.

    Article  Google Scholar 

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Funding

The authors would like to thank the funding agency the Department of Science and Technology—Science and Engineering Research Board, Government of India, New Delhi (grant no: SERB/ECR/2017/000588), for their support.

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Authors and Affiliations

  1. Department of Biotechnology, Sri Venkateswara College of Engineering, Post Bag No. 1, Sriperumbudur Taluk, 602117, Kancheepuram, Tamil Nadu, India

    Hariharan Jayaraman & Ashwin Anandhapadman

  2. Department of Chemical Engineering, Sri Sivasubramaniya Nadar College of Engineering, Rajiv Gandhi Salai (OMR), Kalavakkam, 603110, Tamil Nadu, India

    Nalinkanth Veerabadran Ghone

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Contributions

Study conceptualization, design, material preparation, and data collection and formal analysis were performed by Hariharan Jayaraman. The first draft of the manuscript was written by Hariharan Jayaraman, Ashwin Anandhapadman, and Nalinkanth Veerabadran Ghone. Supervision and funding acquisition were done by Nalinkanth Veerabadran Ghone. All authors read and approved the final manuscript.

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Correspondence to Nalinkanth Veerabadran Ghone.

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Jayaraman, H., Anandhapadman, A. & Ghone, N.V. In Vitro and In Vivo Comparative Analysis of Differentially Expressed Genes and Signaling Pathways in Breast Cancer Cells on Interaction with Mesenchymal Stem Cells. Appl Biochem Biotechnol 195, 401–431 (2023). https://doi.org/10.1007/s12010-022-04119-9

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