Analysis of Non_coding RNA and mRNA-associated ovarian cancer and their potential involvement in cisplatin-resistance phenotype.

Karbalaei Pazoki, Zeinab; Javanmard, Amir Reza; Hosseini, Sayed Mostafa; Irani, Shiva; Mohammad Soltani, Bahram

Analysis of Non_coding RNA and mRNA-associated ovarian cancer and their potential involvement in cisplatin-resistance phenotype.

Document Type : Qualitative Research

Authors

Zeinab Karbalaei Pazoki ¹

Amir reza javanmard ²

sayed mostafa hosseini ³

Shiva Irani ¹

Bahram Mohammad soltani ²

¹ Islamic Azad University, Science and Research Branch

² Tarbiat modares

³ Baqiyatallah University of Medical Sciences

Abstract

Resistance to chemotherapy drugs always has been an obstacle in the definitive treatment of cancers. Therefore, the discovery of molecular events leading to drug resistance improves therapeutic methods. Non-coding RNAs (ncRNAs) are a group of molecules that regulate intracellular events, including carcinogenesis and drug resistance pathways. For example, the competitive network of endogenous ncRNAs (ceRNA) regulates the mRNA expression of target genes by binding to miRNAs and limiting their regulatory effect. So far, limited studies have been reported on the role of ceRNA in drug resistance in ovarian cancer. In this study, large-scale RNAseq sequencing data obtained from cisplatin-resistant and sensitive cells were used to search for ceRNAs that are possible regulators of drug resistance in ovarian cancer. For this purpose, the A2780 sensitive and resistant cisplatin ovarian cancer cell line was selected, and the SRA data prepared by RNAseq method was screened. During this process, lncRNAs, microRNAs and mRNAs with expression changes were separated and classified. In the bioinformatic analysis of resistant and sensitive cells, 16 mRNAs, 10 lncRNAs, and 149 miRNAs were overexpressed, and 622 mRNAs, 263 lncRNAs, and 177 miRNAs were underexpressed. These genes were involved in 57 cellular pathways, and by mapping the regulatory ceRNA network, ZNRF3-AS1-miR-33-DUSP1 and ZNRF3-AS1-miR33-HSPA2 axes were identified as potential ceRNA networks involved in cisplatin-resistant ovarian cancer.

Keywords

Drug resistance-

Cisplatin

Ovarian cancer

ceRNA

20.1001.1.23222115.1401.14.1.11.7

Subjects

Bioinformatics

References
1. Soerjomataram, I., et al., Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. The Lancet, 2012. 380(9856): p. 1840-1850.
2. Berkenblit, A., et al., A phase II trial of weekly docetaxel in patients with platinum-resistant epithelial ovarian, primary peritoneal serous cancer, or fallopian tube cancer. Gynecologic oncology, 2004. 95(3): p. 624-631.
3. Prat, J., New insights into ovarian cancer pathology. Annals of oncology, 2012. 23: p. x111-x117.
4. Jemal, A., et al., Cancer statistics, 2008. CA: a cancer journal for clinicians, 2008. 58(2): p. 71-96.
5. Bast, R.C., B. Hennessy, and G.B. Mills, The biology of ovarian cancer: new opportunities for translation. Nature Reviews Cancer, 2009. 9(6): p. 415-428.
6. Du Bois, A., et al., A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. Journal of the National Cancer Institute, 2003. 95(17): p. 1320-1329.
7. Andrews, P. and S. Howell, Cellular pharmacology of cisplatin: perspectives on mechanisms of acquired resistance. Cancer cells (Cold Spring Harbor, NY: 1989), 1990. 2(2): p. 35-43.
8. Miller, K.D., et al., Cancer statistics for hispanics/latinos, 2018. CA: a cancer journal for clinicians, 2018. 68(6): p. 425-445.
9. Boloker, G., C. Wang, and J. Zhang, Updated statistics of lung and bronchus cancer in United States (2018). Journal of thoracic disease, 2018. 10(3): p. 1158.
10. Rotow, J. and T.G. Bivona, Understanding and targeting resistance mechanisms in NSCLC. Nature Reviews Cancer, 2017. 17(11): p. 637-658.
11. Cree, I.A. and P. Charlton, Molecular chess? Hallmarks of anti-cancer drug resistance. BMC cancer, 2017. 17(1): p. 1-8.
12. Valkov, E., et al., Structure of the Dcp2–Dcp1 mRNA-decapping complex in the activated conformation. Nature structural & molecular biology, 2016. 23(6): p. 574-579.
13. Li, G., et al., The Non-Coding RNAs Inducing Drug Resistance in Ovarian Cancer: A New Perspective for Understanding Drug Resistance. Frontiers in Oncology, 2021. 11.
14. Tay, Y., J. Rinn, and P.P. Pandolfi, The multilayered complexity of ceRNA crosstalk and competition. Nature, 2014. 505(7483): p. 344-352.
15. Lin, M., et al., S100A7 regulates ovarian cancer cell metastasis and chemoresistance through MAPK signaling and is targeted by miR-330-5p. DNA and cell biology, 2018. 37(5): p. 491-500.
16. Xu, K., et al., How powerful are graph neural networks? arXiv preprint arXiv:1810.00826, 2018.
17. Chen, B.-Q., et al., Supercritical fluid-assisted fabrication of indocyanine green-encapsulated silk fibroin nanoparticles for dual-triggered cancer therapy. ACS Biomaterials Science & Engineering, 2018. 4(10): p. 3487-3497.
18. Li, J.-H., et al., starBase v2. 0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data. Nucleic acids research, 2014. 42(D1): p. D92-D97.
19. Jeggari, A., D.S. Marks, and E. Larsson, miRcode: a map of putative microRNA target sites in the long non-coding transcriptome. Bioinformatics, 2012. 28(15): p. 2062-2063.
20. Betel, D., et al., The microRNA. org resource: targets and expression. Nucleic acids research, 2008. 36(suppl_1): p. D149-D153.
21. Shannon, P., et al., Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome research, 2003. 13(11): p. 2498-2504.
22. Zhang, X.-w., et al., Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance. Biochemical and biophysical research communications, 2015. 462(3): p. 227-232.
23. Hu, G., Personalized neural embeddings for collaborative filtering with text. arXiv preprint arXiv:1903.07860, 2019.
24. Wang, S., et al., The role of microRNA in cisplatin resistance or sensitivity. Expert Opinion on Therapeutic Targets, 2020. 24(9): p. 885-897.
25. Bartel, D.P., MicroRNAs: genomics, biogenesis, mechanism, and function. cell, 2004. 116(2): p. 281-297.
26. Kong, X., et al., Analysis of lncRNA, miRNA and mRNA-associated ceRNA networks and identification of potential drug targets for drug-resistant non-small cell lung cancer. Journal of Cancer, 2020. 11(11): p. 3357.
27. Ju, C., et al., LncRNA SNHG5 promotes the progression of osteosarcoma by sponging the miR-212-3p/SGK3 axis. Cancer cell international, 2018. 18(1): p. 1-13.
28. Guo, L., et al., Construction and Analysis of a ceRNA Network Reveals Potential Prognostic Markers in Colorectal Cancer. Frontiers in Genetics, 2020. 11: p. 418.
29. Chen, H.-Y., et al., miR-103/107 prolong Wnt/β-catenin signaling and colorectal cancer stemness by targeting Axin2. Scientific reports, 2019. 9(1): p. 1-13.
30. Yu, Q., et al., MiR-103/107 induces tumorigenicity in bladder cancer cell by suppressing PTEN. Eur Rev Med Pharmacol Sci, 2018. 22(24): p. 8616-8623.
31. Amaar, Y.G. and M.E. Reeves, RASSF1C regulates miR-33a and EMT marker gene expression in lung cancer cells. Oncotarget, 2019. 10(2): p. 123.
32. Chen, R., et al., Histone methyltransferase SETD2: a potential tumor suppressor in solid cancers. Journal of Cancer, 2020. 11(11): p. 3349.
33. Lee, S., J. Rauch, and W. Kolch, Targeting MAPK signaling in cancer: mechanisms of drug resistance and sensitivity. International journal of molecular sciences, 2020. 21(3): p. 1102.
34. Liu, R., et al., PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers. Cell death & disease, 2020. 11(9): p. 1-12.
35. Teng, F., et al., DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer. Oncology reports, 2018. 40(3): p. 1203-1222.
36. Tice, D.A., I. Soloviev, and P. Polakis, Activation of the Wnt pathway interferes with serum response element-driven transcription of immediate early genes. Journal of Biological Chemistry, 2002. 277(8): p. 6118-6123.
37. Giulino-Roth, L., et al., Inhibition of Hsp90 suppresses PI3K/AKT/mTOR signaling and has antitumor activity in Burkitt lymphoma. Molecular cancer therapeutics, 2017. 16(9): p. 1779-1790.