Silencing of miR-1246 Induces Cell Cycle Arrest and Apoptosis in Cisplatin-Resistant Ovarian Cancer Cells by Promoting ZNF23 Transcription

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent/Cloud Rent for 48h to view Buy Cloud Access for unlimited viewing via different devices Synchronizing in the ReadCube Cloud Printing and saving restrictions apply Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Abstract of Original Article

Received: April 14, 2021
Accepted: October 06, 2021
Published online: December 17, 2021

Number of Print Pages: 13
Number of Figures: 6
Number of Tables: 1

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: https://www.karger.com/CGR

Abstract

Ovarian cancer (OC) is the most frequent cause of death among patients with gynecologic malignancies. In recent years, the development of cisplatin (DDP) resistance has become an important reason for the poor prognosis of OC patients. Therefore, it is vital to explore the mechanism of DDP resistance in OC. In this study, microRNA-1246 (miR-1246) expression in OC and DDP-resistant OC cells was determined by RT-qPCR, and chemosensitivity to DDP was assessed by the CCK-8 assay. A dual-luciferase reporter assay was performed to confirm the interaction between miR-1246 and zinc finger 23 (ZNF23), while changes in ZNF23 expression were monitored by RT-qPCR, immunofluorescence, and western blot assays. Moreover, cell proliferation, cycle phase, and apoptosis were determined by EdU staining, flow cytometry, TUNEL staining, and Hoechst staining. Our data showed that miR-1246 was highly expressed in DDP-resistant OVCAR-3 and TOV-112D cells. Functionally, overexpression of miR-1246 markedly enhanced DDP resistance and cell proliferation, and suppressed cell cycle arrest and apoptosis of OC cells. Inhibition of miR-1246 expression significantly attenuated DDP resistance and cell proliferation, and increased cell cycle arrest and apoptosis in DDP-resistant OC cells. Furthermore, ZNF23 was identified as a target gene of miR-1246, and ZNF23 protein expression was notably downregulated in DDP-resistant OC cells. Moreover, overexpression of miR-1246 significantly downregulated the ZNF23 levels in OVCAR-3 and TOV-112D cells, and inhibition of miR-1246 upregulated the ZNF23 levels in the DDP-resistant OVCAR-3 and TOV-112D cells. In conclusion, miR-1246 might be a novel regulator of DDP-resistant OC that functions by regulating ZNF23 expression in DDP-resistant cells, as well as cell proliferation, cell cycle progression, and apoptosis.

© 2021 S. Karger AG, Basel

References Abbastabar M, Kheyrollah M, Azizian K, Bagherlou N, Tehrani SS, Maniati M, et al. Multiple functions of p27 in cell cycle, apoptosis, epigenetic modification and transcriptional regulation for the control of cell growth: A double-edged sword protein. DNA Repair (Amst). 2018;69:63–72. Al Hadidi S, Aburahma A, Badami S, Upadhaya S. PARP (Poly(ADP-Ribose) Polymerase) Inhibitors in Platinum-Sensitive Recurrent Ovarian Cancer: A Meta-Analysis of Randomized Controlled Trials. Oncol Res Treat. 2018;41(4):226–35. Bauersfeld SP, Kessler CS, Wischnewsky M, Jaensch A, Steckhan N, Stange R, et al. The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study. BMC Cancer. 2018;18(1):476. Bhagirath D, Yang TL, Bucay N, Sekhon K, Majid S, Shahryari V, et al. microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer. Cancer Res. 2018;78(7):1833–44. Chen J. The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression. Cold Spring Harb Perspect Med. 2016;6(3):a026104. Chen J, Yao D, Zhao S, He C, Ding N, Li L, et al. miR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2. Arch Gynecol Obstet. 2014;290(4):725–32. Chen X, Lu P, Wu Y, Wang DD, Zhou S, Yang SJ, et al. miRNAs-mediated cisplatin resistance in breast cancer. Tumour Biol. 2016;37(10):12905–13. Coleman RL, Spirtos NM, Enserro D, Herzog TJ, Sabbatini P, Armstrong DK, et al. Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer. N Engl J Med. 2019;381(20):1929–39. Cui Y, Wu F, Tian D, Wang T, Lu T, Huang X, et al. miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8. Oncol Rep. 2018;39(4):1649–57. Du P, Lai YH, Yao DS, Chen JY, Ding N. Downregulation of microRNA-1246 inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting thrombospondin-2. Oncol Lett. 2019;18(3):2491–9. Elies A, Rivière S, Pouget N, Becette V, Dubot C, Donnadieu A, et al. The role of neoadjuvant chemotherapy in ovarian cancer. Expert Rev Anticancer Ther. 2018;18(6):555–66. Fridrichova I, Zmetakova I. MicroRNAs Contribute to Breast Cancer Invasiveness. Cells. 2019;8(11):1361. Gong S, Chen Y, Meng F, Zhang Y, Li C, Zhang G, et al. Roflumilast enhances cisplatin-sensitivity and reverses cisplatin-resistance of ovarian cancer cells via cAMP/PKA/CREB-FtMt signalling axis. Cell Prolif. 2018;51(5):e12474. Huang C, Jia Y, Yang S, Chen B, Sun H, Shen F, et al. Characterization of ZNF23, a KRAB-containing protein that is downregulated in human cancers and inhibits cell cycle progression. Exp Cell Res. 2007;313(2):254–63. Huang C, Yang S, Ge R, Sun H, Shen F, Wang Y. ZNF23 induces apoptosis in human ovarian cancer cells. Cancer Lett. 2008;266(2):135–43. Jin P, Liu Y, Wang R. STAT3 regulated miR-216a promotes ovarian cancer proliferation and cisplatin resistance. Biosci Rep. 2018;38(4):BSR20180547. Kaczanowski S. Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging. Phys Biol. 2016;13(3):031001. Katifelis H, Lyberopoulou A, Mukha I, Vityuk N, Grodzyuk G, Theodoropoulos GE, et al. Ag/Au bimetallic nanoparticles induce apoptosis in human cancer cell lines via P53, CASPASE-3 and BAX/BCL-2 pathways. Artif Cells Nanomed Biotechnol. 2018;46(Suppl 3):S389–398. Li L, Ma Y, Liu S, Xu X. Metabonomics study of the serum from ovarian cancer patients. Eur J Gynaecol Oncol. 2019;40(5):722–7. Li XJ, Ren ZJ, Tang JH, Yu Q. Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer. Cell Physiol Biochem. 2017;44(5):1741–8. Li X, Chen W, Jin Y, Xue R, Su J, Mu Z, et al. miR-142-5p enhances cisplatin-induced apoptosis in ovarian cancer cells by targeting multiple anti-apoptotic genes. Biochem Pharmacol. 2019;161:98–112. Lin SS, Peng CY, Liao YW, Chou MY, Hsieh PL, Yu CC. miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral Carcinomas. Cancers (Basel). 2018;10(8):272. Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018;141(4):1202–7. Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY. Ovarian cancer. Nat Rev Dis Primers. 2016;2:16061. McQuade RM, Stojanovska V, Bornstein JC, Nurgali K. PARP inhibition in platinum-based chemotherapy: Chemopotentiation and neuroprotection. Pharmacol Res. 2018;137:104–13. Menon U, Karpinskyj C, Gentry-Maharaj A. Ovarian Cancer Prevention and Screening. Obstet Gynecol. 2018;131(5):909–27. Niu Q, Liu Z, Gao J, Wang Q. MiR-338-3p Enhances Ovarian Cancer Cell Sensitivity to Cisplatin by Downregulating WNT2B. Yonsei Med J. 2019;60(12):1146–56. Orr B, Edwards RP. Diagnosis and Treatment of Ovarian Cancer. Hematol Oncol Clin North Am. 2018;32(6):943–64. Qin XB, Yu SR, Zhou LL, Shi MQ, Hu Y, Xu Xy, et al. Cisplatin-resistant lung cancer cell-derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100-5p-dependent manner. Int J Nanomedicine. 2017;15(12):3721–33. Roett MA, Evans P. Ovarian cancer: an overview. Am Fam Physician. 2009;80(6):609–16. Rooth C. Ovarian cancer: risk factors, treatment and management. Br J Nurs. 2013;22(17):S23–30. Rossi A, Di Maio M. Platinum-based chemotherapy in advanced non-small-cell lung cancer: optimal number of treatment cycles. Expert Rev Anticancer Ther. 2016;16(6):653–60. Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16(3):203–22. Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, Ghaffari SH. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J Cell Physiol. 2019;234(5):5451–65. Shi Y, Zheng L, Luo G, Wei J, Zhang J, Yu Y, et al. Expression of zinc finger 23 gene in human hepatocellular carcinoma. Anticancer Res. 2011;31(10):3595–9. Shi Y, Wang Z, Zhu X, Chen L, Ma Y, Wang J, et al. Exosomal miR-1246 in serum as a potential biomarker for early diagnosis of gastric cancer. Int J Clin Oncol. 2020;25(1):89–99. Stewart C, Ralyea C, Lockwood S. Ovarian Cancer: An Integrated Review. Semin Oncol Nurs. 2019;35(2):151–6. Todeschini P, Salviato E, Paracchini L, Ferracin M, Petrillo M, Zanotti L, et al. Circulating miRNA landscape identifies miR-1246 as promising diagnostic biomarker in high-grade serous ovarian carcinoma: A validation across two independent cohorts. Cancer Lett. 2017;388:320–7. Wang C, Wang S, Ma F, Zhang W. miRNA328 overexpression confers cisplatin resistance in nonsmall cell lung cancer via targeting of PTEN. Mol Med Rep. 2018;18(5):4563–70. Wang LH, Wu CF, Rajasekaran N, Shin YK. Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview. Cell Physiol Biochem. 2018;51(6):2647–93. Wang S, Zeng Y, Zhou JM, Nie SL, Peng Q, Gong J, et al. MicroRNA-1246 promotes growth and metastasis of colorectal cancer cells involving CCNG2 reduction. Mol Med Rep. 2016;13(1):273–80. Wei C, Li Y, Huang K, Li G, He M. Exosomal miR-1246 in body fluids is a potential biomarker for gastrointestinal cancer. Biomark Med. 2018;12(10):1185–96. Xiao F, Li Y, Wan Y, Xue M. MircroRNA-139 sensitizes ovarian cancer cell to cisplatin-based chemotherapy through regulation of ATP7A/B. Cancer Chemother Pharmacol. 2018;81(5):935–47. Xu ZH, Yao TZ, Liu W. miR-378a-3p sensitizes ovarian cancer cells to cisplatin through targeting MAPK1/GRB2. Biomed Pharmacother. 2018;107:1410–7. Yang F, Xiong H, Duan L, Li Q, Li X, Zhou Y. MiR-1246 Promotes Metastasis and Invasion of A549 cells by Targeting GSK-3β‒Mediated Wnt/β-Catenin Pathway. Cancer Res Treat. 2019;51(4):1420–9. Yang P, Wang Y, Macfarlan TS. The Role of KRAB-ZFPs in Transposable Element Repression and Mammalian Evolution. Trends Genet. 2017;33(11):871–81. Yin C, Zheng X, Xiang H, Li H, Gao M, Meng X, et al. Differential expression profile analysis of cisplatinregulated miRNAs in a human gastric cancer cell line. Mol Med Rep. 2019;20(2):1966–76. You F, Luan H, Sun D, Cui T, Ding P, Tang H, et al. miRNA-106a Promotes Breast Cancer Cell Proliferation, Clonogenicity, Migration, and Invasion Through Inhibiting Apoptosis and Chemosensitivity. DNA Cell Biol. 2019;38(2):198–207. Yuan D, Xu J, Wang J, Pan Y, Fu J, Bai Y, et al. Extracellular miR-1246 promotes lung cancer cell proliferation and enhances radioresistance by directly targeting DR5. Oncotarget. 2016;7(22):32707–22. Zhang X, Ding C, Tian H, Dong X, Meng X, Zhu W, et al. ZNF23 Suppresses Cutaneous Melanoma Cell Malignancy via Mitochondria-Dependent Pathway. Cell Physiol Biochem. 2017;43(1):147–57. Zhang Y, Huang S, Guo Y, Li L. MiR-1294 confers cisplatin resistance in ovarian Cancer cells by targeting IGF1R. Biomed Pharmacother. 2018;106:1357–63. Zhang Z, Zhang L, Wang B, Wei R, Wang Y, Wan J, et al. MiR-337-3p suppresses proliferation of epithelial ovarian cancer by targeting PIK3CA and PIK3CB. Cancer Lett. 2020;469:54–67. Article / Publication Details

First-Page Preview

Abstract of Original Article

Received: April 14, 2021
Accepted: October 06, 2021
Published online: December 17, 2021

Number of Print Pages: 13
Number of Figures: 6
Number of Tables: 1

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: https://www.karger.com/CGR

留言 (0)

沒有登入
gif