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Upregulation of long noncoding RNA XIST has anticancer effects on ovarian cancer through sponging miR-106a

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Abstract

Ovarian cancer (OC) is a highly malignant tumor. X inactive specific transcript (XIST) was identified as a cancer-related gene, while its therapeutic effect in OC was poorly defined. The present study was designed to investigate the effectual corollary of the lncRNA XIST in OC. RT-qPCR was used to detect the XIST and miR-106a expression levels of OC tissues and cell lines. OC cell apoptosis and proliferation were detected by flow cytometry, colony formation, and CCK-8 assays. Moreover, bioinformatics analysis was used to predict the targeted miRNA of XIST. The dual-luciferase reporter and RNA pull-down assays were then used to verify the interaction between miR-106a and XIST. OC xenograft nude mice were raised to measure tumor growth. Notably, OC tissues and cells exhibited low XIST levels and high miR-106a levels. The XIST upregulation decreased the OVCAR3 and CAOV3 cell proliferation and inversely promoted cell apoptosis. miR-106a targeted the XIST. Also, the miR-106a overexpression reversed the inhibitory effects of XIST on OC cell proliferation and apoptosis. Our in vivo results suggested that XIST was involved in tumor growth deceleration, while the miR-106a reversed the effect. To conclusion, the present study demonstrated that XIST suppressed OC development via sponging miR-106a both in vitro and in vivo.

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Data accessibility

The datasets used during the current study are available from the corresponding author on a reasonable request.

References

  1. Cunnea P, Gowers S, Moore JE Jr, Drakakis E, Boutelle M, Fotopoulou C. Review article: novel technologies in the treatment and monitoring of advanced and relapsed epithelial ovarian cancer. Converg Sci Phys Oncol. 2017. https://doi.org/10.1088/2057-1739/aa5cf1.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Luvero D, Milani A, Ledermann JA. Treatment options in recurrent ovarian cancer: latest evidence and clinical potential. Ther Adv Med Oncol. 2014;6:229–39.

    Article  CAS  Google Scholar 

  3. Armbruster S, Coleman RL, Rauh-Hain JA. Management and treatment of recurrent epithelial ovarian cancer. Hematol Oncol Clin N Am. 2018;32:965–82.

    Article  Google Scholar 

  4. Schmid BC, Oehler MK. New perspectives in ovarian cancer treatment. Maturitas. 2014;77:128–36.

    Article  CAS  Google Scholar 

  5. Feng W, Marquez RT, Lu Z, et al. Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation. Cancer. 2008;112:1489–502.

    Article  CAS  Google Scholar 

  6. Ratner E, Lu L, Boeke M, et al. A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk. Cancer Res. 2010;70:6509–15.

    Article  CAS  Google Scholar 

  7. Zhang L, Ma T, Brozick J, et al. Effects of Kras activation and Pten deletion alone or in combination on MUC1 biology and epithelial-to-mesenchymal transition in ovarian cancer. Oncogene. 2016;35:5010–20.

    Article  CAS  Google Scholar 

  8. Scott MS, Ono M. From snoRNA to miRNA: dual function regulatory non-coding RNAs. Biochimie. 2011;93:1987–92.

    Article  CAS  Google Scholar 

  9. Zhu J, Kong F, Xing L, Jin Z, Li Z. Prognostic and clinicopathological value of long noncoding RNA XIST in cancer. Clin Chim Acta. 2018;479:43–7.

    Article  CAS  Google Scholar 

  10. Du Y, Weng XD, Wang L, et al. LncRNA XIST acts as a tumor suppressor in prostate cancer through sponging miR-23a to modulate RKIP expression. Oncotarget. 2017;8:94358–70.

    Article  Google Scholar 

  11. Gao W, Gao J, Chen L, Ren Y, Ma J. Targeting XIST induced apoptosis of human osteosarcoma cells by activation of NF-kB/PUMA signal. Bioengineered. 2019;10:261–70.

    Article  Google Scholar 

  12. Hu Y, Mei XQ, Tang D. Long non-coding RNA XIST is down-regulated and correlated to better prognosis in ovarian cancer. Math Biosci Eng. 2020;17:2070–81.

    Article  Google Scholar 

  13. Rupaimoole R, Calin GA, Lopez-Berestein G, Sood AK. miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov. 2016;6:235–46.

    Article  CAS  Google Scholar 

  14. Cai ZH, Chen LM, Liang YJ, et al. Experimental study on the inhibition effect of miR-106a inhibitor on tumor growth of ovarian cancer xenografts mice. Asian Pac J Trop Med. 2016;9:698–701.

    Article  CAS  Google Scholar 

  15. Wang C, Qi S, Xie C, Li C, Wang P, Liu D. Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p. J Gynecol Oncol. 2018;29:e99.

    Article  CAS  Google Scholar 

  16. Huarte M. The emerging role of lncRNAs in cancer. Nat Med. 2015;21:1253–61.

    Article  CAS  Google Scholar 

  17. Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017;36:5661–7.

    Article  CAS  Google Scholar 

  18. Yang G, Lu X, Yuan L. LncRNA: a link between RNA and cancer. Biochim Biophys Acta. 2014;1839:1097–109.

    Article  CAS  Google Scholar 

  19. Zhou Q, Hu W, Zhu W, et al. Long non coding RNA XIST as a prognostic cancer marker—a meta-analysis. Clin Chim Acta. 2018;482:1–7.

    Article  CAS  Google Scholar 

  20. Chen DL, Chen LZ, Lu YX, et al. Long noncoding RNA XIST expedites metastasis and modulates epithelial–mesenchymal transition in colorectal cancer. Cell Death Dis. 2017;8:e3011.

    Article  CAS  Google Scholar 

  21. Cui CL, Li YN, Cui XY, Wu X. lncRNA XIST promotes the progression of laryngeal squamous cell carcinoma by sponging miR144 to regulate IRS1 expression. Oncol Rep. 2020;43:525–35.

    CAS  PubMed  Google Scholar 

  22. Cheng Z, Luo C, Guo Z. LncRNA-XIST/microRNA-126 sponge mediates cell proliferation and glucose metabolism through the IRS1/PI3K/Akt pathway in glioma. J Cell Biochem. 2020;121:2170–83.

    Article  CAS  Google Scholar 

  23. Huang KC, Rao PH, Lau CC, et al. Relationship of XIST expression and responses of ovarian cancer to chemotherapy. Mol Cancer Ther. 2002;1:769–76.

    CAS  PubMed  Google Scholar 

  24. Han Q, Li L, Liang H, Li Y, Xie J, Wang Z. Downregulation of lncRNA X inactive specific transcript (XIST) suppresses cell proliferation and enhances radiosensitivity by upregulating mir-29c in nasopharyngeal carcinoma cells. Med Sci Monit. 2017;23:4798–807.

    Article  Google Scholar 

  25. Kong Q, Zhang S, Liang C, et al. LncRNA XIST functions as a molecular sponge of miR-194-5p to regulate MAPK1 expression in hepatocellular carcinoma cell. J Cell Biochem. 2018;119:4458–68.

    Article  CAS  Google Scholar 

  26. Li X, Hou L, Yin L, Zhao S. LncRNA XIST interacts with miR-454 to inhibit cells proliferation, epithelial mesenchymal transition and induces apoptosis in triple-negative breast cancer. J Biosci. 2020;45:1–11.

    Article  CAS  Google Scholar 

  27. Pan YJ, Zhuang Y, Zheng JN, Pei DS. MiR-106a: promising biomarker for cancer. Bioorg Med Chem Lett. 2016;26:5373–7.

    Article  CAS  Google Scholar 

  28. Jiang Y, Wu Y, Greenlee AR, et al. miR-106a-mediated malignant transformation of cells induced by anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide. Toxicol Sci. 2011;119:50–60.

    Article  CAS  Google Scholar 

  29. Qin Y, Huo Z, Song X, Chen X, Tian X, Wang X. mir-106a regulates cell proliferation and apoptosis of colon cancer cells through targeting the PTEN/PI3K/AKT signaling pathway. Oncol Lett. 2018;15:3197–201.

    PubMed  Google Scholar 

  30. Grunewald T, Ledermann JA. Targeted therapies for ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2017;41:139–52.

    Article  Google Scholar 

  31. Amini-Farsani Z, Sangtarash MH, Shamsara M, Teimori H. MiR-221/222 promote chemoresistance to cisplatin in ovarian cancer cells by targeting PTEN/PI3K/AKT signaling pathway. Cytotechnology. 2018;70:203–13.

    Article  CAS  Google Scholar 

  32. Liu HY, Zhang YY, Zhu BL, et al. MiR-203a-3p regulates the biological behaviors of ovarian cancer cells through mediating the Akt/GSK-3beta/Snail signaling pathway by targeting ATM. J Ovarian Res. 2019;12:60.

    Article  Google Scholar 

  33. Zhou J, Zhang C, Zhou B, Jiang D. miR-183 modulated cell proliferation and apoptosis in ovarian cancer through the TGF-beta/Smad4 signaling pathway. Int J Mol Med. 2019;43:1734–46.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work is financially supported by the National Natural Science Foundation of China (81571797), Natural Science Foundation of Jiangsu, China (BK20151352), Taizhou People’s Hospital Medical Innovation Team Foundation, China (CXTDA201901), and Scientific Research Foundation of Taizhou People’s Hospital (ZL201734/ZL201726), China.

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Author notes

  1. Ting Guo and Donglan Yuan contributed equally to this work.

Authors and Affiliations

  1. Institute of Clinical Medicine, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, 225300, Jiangsu, China

    Ting Guo & Guangyao Mao

  2. The Department of Obstetrics and Gynecology, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, 225300, Jiangsu, China

    Donglan Yuan & Dandan Zhu

  3. The Department of Infectious Disease, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, 225300, Jiangsu, China

    Wei Zhang

  4. Emergency Department, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, 225300, Jiangsu, China

    Aifang Xiao, Wenjuan Jiang & Jun Wang

  5. Clinical Laboratory, Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, 225300, Jiangsu, China

    Mei Lin

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  1. Ting Guo
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  2. Donglan Yuan
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  3. Wei Zhang
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Corresponding authors

Correspondence to Mei Lin or Jun Wang.

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Research involving human/animal participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of Taizhou People’s Hospital Affiliated to Nantong University (No. 202004701).

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Guo, T., Yuan, D., Zhang, W. et al. Upregulation of long noncoding RNA XIST has anticancer effects on ovarian cancer through sponging miR-106a. Human Cell 34, 579–587 (2021). https://doi.org/10.1007/s13577-020-00469-w

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  • DOI: https://doi.org/10.1007/s13577-020-00469-w

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