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Hsa_circ_0074269-mediated Upregulation of TUFT1 Through miR-485-5p Increases Cisplatin Resistance in Cervical Cancer

  • Gynecologic Oncology: Original Article
  • Published:
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Abstract

Most cervical cancer patients are prone to developing acquired cisplatin (DDP) resistance. Hsa_circ_0074269 (circ_0074269) plays a promoting role in cervical cancer, but whether circ_0074269 mediates cervical cancer resistance to DDP is unclear. Expression of circ_0074269 was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The half-maximal inhibitory concentration (IC50) value, viability, proliferation, colony formation, migration, and apoptosis of DDP-resistant cervical cancer cells were determined. The molecular mechanisms associated with circ_0074269 were predicted by bioinformatics analysis and confirmed by dual-luciferase reporter and RIP assays. Xenograft assay was conducted to validate the effect of circ_0074269 on DDP resistance in vivo. Exosomes were isolated by ultracentrifugation. Circ_0074269 was overexpressed in DDP-resistant cervical cancer samples and cells. Silencing of circ_0074269 elevated DDP sensitivity, repressed DDP-resistant cervical cancer cell proliferation, and induced DDP-resistant cervical cancer cell apoptosis in vivo and in vitro and curbed DDP-resistant cervical cancer cell migration in vitro. And circ_0074269 could regulate DDP resistance via regulating TUFT1 expression via sponging miR-485-5p. More strikingly, circ_0074269 was also overexpressed in exosomes from DDP-resistant cervical cancer cells, and circ_0074269 could be delivered via exosomes. Circ_0074269 facilitated DDP resistance via elevating TUFT1 expression via sponging miR-485-5p, proving novel evidence to offer circ_0074269 as a target for cervical cancer treatment.

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References

  1. de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8(2):e180–90.

    Article  Google Scholar 

  2. Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013;382(9895):889–99.

    Article  Google Scholar 

  3. Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019;393(10167):169–82.

    Article  Google Scholar 

  4. Shieh KR, Huang A, Xu Y. Response to Immune checkpoint inhibitor treatment in advanced cervical cancer and biomarker study. Front Med. 2021;8:669587.

    Article  Google Scholar 

  5. Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, et al. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2019;37(17):1470–8.

    Article  CAS  Google Scholar 

  6. Shen D-W, Pouliot LM, Hall MD, Gottesman MM. Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol Rev. 2012;64(3):706–21.

    Article  CAS  Google Scholar 

  7. Makovec T. Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol. 2019;53(2):148–58.

    Article  CAS  Google Scholar 

  8. Tchounwou PB, Dasari S, Noubissi FK, Ray P, Kumar S. Advances in our understanding of the molecular mechanisms of action of cisplatin in cancer therapy. J Exp Pharmacol. 2021;13:303–28.

    Article  Google Scholar 

  9. Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P, Wu M. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer. 2017;16(1):94.

    Article  Google Scholar 

  10. Verduci L, Tarcitano E. CircRNAs: role in human diseases and potential use as biomarkers. Cell Death Dis. 2021;12(5):468.

    Article  CAS  Google Scholar 

  11. Cui C, Yang J, Li X, Liu D, Fu L, Wang X. Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance. Mol Cancer. 2020;19(1):58.

    Article  Google Scholar 

  12. Jeyaraman S, Hanif EAM, Ab Mutalib NS, Jamal R, Abu N. Circular RNAs: potential regulators of treatment resistance in human cancers. Front Genet. 2019;10:1369.

    Article  CAS  Google Scholar 

  13. Chen M, Ai G, Zhou J, Mao W, Li H, Guo J. circMTO1 promotes tumorigenesis and chemoresistance of cervical cancer via regulating miR-6893. Biomed Pharmacother. 2019;117:109064.

    Article  CAS  Google Scholar 

  14. Guo J, Chen M, Ai G, Mao W, Li H, Zhou J. Hsa_circ_0023404 enhances cervical cancer metastasis and chemoresistance through VEGFA and autophagy signaling by sponging miR-5047. Biomed Pharmacother. 2019;115:108957.

    Article  CAS  Google Scholar 

  15. Zhu Y, Jiang X, Zhang S. Hsa_circ_103973 acts as a sponge of miR-335 to promote cervical cancer progression. Onco Targets Ther. 2020;13:1777–86.

    Article  CAS  Google Scholar 

  16. Verduci L, Strano S, Yarden Y, Blandino G. The circRNA-microRNA code: emerging implications for cancer diagnosis and treatment. Mol Oncol. 2019;13(4):669–80.

    Article  Google Scholar 

  17. Lou C, Xiao M, Cheng S, Lu X, Jia S, Ren Y, Li Z. MiR-485–3p and miR-485–5p suppress breast cancer cell metastasis by inhibiting PGC-1α expression. Cell Death Dis. 2016;7(3):e2159.

    Article  CAS  Google Scholar 

  18. Tu J, Zhao Z, Xu M, Chen M, Weng Q, Ji J. LINC00460 promotes hepatocellular carcinoma development through sponging miR-485–5p to up-regulate PAK1. Biomed Pharmacother. 2019;118:109213.

    Article  CAS  Google Scholar 

  19. Liu H, Hu G, Wang Z, Liu Q, Zhang J, Chen Y, Huang Y, Xue W, Xu Y, Zhai W. circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis. Theranostics. 2020;10(23):10791–807.

    Article  CAS  Google Scholar 

  20. Qiao HF, Liu YL, You J, Zheng YL, Chen LP, Lu XY, Du L, Shan F, Liu MH. G-5555 synergized miR-485–5p to alleviate cisplatin resistance in ovarian cancer cells via Pi3k/Akt signaling pathway. J Reprod Immunol. 2020;140:103129.

    Article  CAS  Google Scholar 

  21. Lin XJ, He CL, Sun T, Duan XJ, Sun Y, Xiong SJ. hsa-miR-485-5p reverses epithelial to mesenchymal transition and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma. Int J Mol Med. 2017;40(1):83–9.

    Article  CAS  Google Scholar 

  22. Ou R, Lv J, Zhang Q, Lin F, Zhu L, Huang F, Li X, Li T, Zhao L, Ren Y, et al. circAMOTL1 motivates AMOTL1 expression to facilitate cervical cancer growth. Mol Ther Nucleic Acids. 2020;19:50–60.

    Article  CAS  Google Scholar 

  23. Zhao D, Zhang H, Long J, Li M. LncRNA SNHG7 functions as an oncogene in cervical cancer by sponging miR-485–5p to modulate JUND Expression. Onco Targets Ther. 2020;13:1677–89.

    Article  CAS  Google Scholar 

  24. Deutsch D, Palmon A, Fisher LW, Kolodny N, Termine JD, Young MF. Sequencing of bovine enamelin (“tuftelin”) a novel acidic enamel protein. J Biol Chem. 1991;266(24):16021–8.

    Article  CAS  Google Scholar 

  25. Luo X, Wei J, Yang FL, Pang XX, Shi F, Wei YX, Liao BY, Wang JL. Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis. Cancer Cell Int. 2019;19:323.

    Article  CAS  Google Scholar 

  26. Liu W, Han J, Shi S, Dai Y, He J. TUFT1 promotes metastasis and chemoresistance in triple negative breast cancer through the TUFT1/Rab5/Rac1 pathway. Cancer Cell Int. 2019;19:242.

    Article  Google Scholar 

  27. Yang S, Shi F, Du Y, Wang Z, Feng Y, Song J, Liu Y. Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163. Cancer Cell Int. 2020;20:343.

    Article  CAS  Google Scholar 

  28. Luo KW, Zhu XH, Zhao T, Zhong J, Gao HC, Luo XL, Huang WR. EGCG enhanced the anti-tumor effect of doxorubicine in bladder cancer via NF-κB/MDM2/p53 Pathway. Front Cell Dev Biol. 2020;8:606123.

    Article  Google Scholar 

  29. Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019;18(1):75.

    Article  Google Scholar 

  30. Zhu H, Luo H, Zhang W, Shen Z, Hu X, Zhu X. Molecular mechanisms of cisplatin resistance in cervical cancer. Drug Des Devel Ther. 2016;10:1885–95.

    Article  CAS  Google Scholar 

  31. Xu T, Wang M, Jiang L, Ma L, Wan L, Chen Q, Wei C, Wang Z. CircRNAs in anticancer drug resistance: recent advances and future potential. Mol Cancer. 2020;19(1):127.

    Article  CAS  Google Scholar 

  32. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333–8.

    Article  CAS  Google Scholar 

  33. Dai Y, Xie F, Chen Y. Reduced levels of miR-485–5p in HPV-infected cervical cancer promote cell proliferation and enhance invasion ability. FEBS Open Bio. 2020;10(7):1348–61.

    Article  CAS  Google Scholar 

  34. Ou R, Lv J, Zhang Q, Lin F, Zhu L, Huang F, Li X, Li T, Zhao L, Ren Y, et al. circAMOTL1 motivates AMOTL1 expression to facilitate cervical cancer growth. Onco Targets Ther. 2020;19:50–60.

    CAS  Google Scholar 

  35. Zhao D, Zhang H, Long J, Li M. LncRNA SNHG7 functions as an oncogene in cervical cancer by sponging miR-485-5p to modulate JUND expression. FEBS Open Bio. 2020;13:1677–89.

    CAS  Google Scholar 

  36. Zhou B, Zhan H, Tin L, Liu S, Xu J, Dong Y, Li X, Wu L, Guo W. TUFT1 regulates metastasis of pancreatic cancer through HIF1-Snail pathway induced epithelial-mesenchymal transition. Cancer Lett. 2016;382(1):11–20.

    Article  CAS  Google Scholar 

  37. Liu H, Zhu J, Mao Z, Zhang G, Hu X, Chen F. Tuft1 promotes thyroid carcinoma cell invasion and proliferation and suppresses apoptosis through the Akt-mTOR/GSK3β signaling pathway. Am J Transl Res. 2018;10(12):4376–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Wu MN, Zheng WJ, Ye WX, Wang L, Chen Y, Yang J, Yao DF, Yao M. Oncogenic tuftelin 1 as a potential molecular-targeted for inhibiting hepatocellular carcinoma growth. World J Gastroenterol. 2021;27(23):3327–41.

    Article  CAS  Google Scholar 

  39. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478).

  40. Luo Y, Gui R. Circulating exosomal circFoxp1 confers cisplatin resistance in epithelial ovarian cancer cells. J Gynecol Oncol. 2020;31(5):e75.

  41. Zhang PF, Gao C, Huang XY, Lu JC, Guo XJ, Shi GM, Cai JB, Ke AW. Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma. J Gynecol Oncol. 2020;19(1):110.

    CAS  Google Scholar 

  42. Ding C, Yi X, Chen X, Wu Z, You H, Chen X, Zhang G, Sun Y, Bu X, Wu X, et al. Warburg effect-promoted exosomal circ_0072083 releasing up-regulates NANGO expression through multiple pathways and enhances temozolomide resistance in glioma. J Exp Clin Cancer Res. 2021;40(1):164.

    Article  CAS  Google Scholar 

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Author notes

  1. Jing Chen and Sheng Wu contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Jingjiang People’s Hospital, Taizhou City, 214500, Jiangsu, China

    Jing Chen, Sheng Wu, Jue Wang & Yu Sha

  2. Department of General Surgery, Jingjiang People’s Hospital, No.9-5, Kejixincun, Jingjiang, Taizhou City, 214500, Jiangsu Province, China

    Yong Ji

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  1. Jing Chen
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Correspondence to Yong Ji.

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Written informed consents were obtained from all participants and this study was permitted by the Ethics Committee of Jingjiang People’s Hospital.

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Chen, J., Wu, S., Wang, J. et al. Hsa_circ_0074269-mediated Upregulation of TUFT1 Through miR-485-5p Increases Cisplatin Resistance in Cervical Cancer. Reprod. Sci. 29, 2236–2250 (2022). https://doi.org/10.1007/s43032-022-00855-9

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  • DOI: https://doi.org/10.1007/s43032-022-00855-9

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