MiR-4284 inhibits sensitivity to paclitaxel in human ovarian carcinoma SKOV3ip1 and HeyA8 cells by targeting DMC1

Anticancer Drugs. 2022 Sep 1;33(8):701-709. doi: 10.1097/CAD.0000000000001314. Epub 2022 Aug 10.

Abstract

An increasing number of studies have confirmed that microRNAs (miRNAs) are involved in various biological processes, including tumor growth and drug resistance. MiR-4284 has been proved to be abnormally regulated in several cancers, but the function of miR-4284 in ovarian carcinoma (OC) is unclear. Paclitaxel resistance is a key obstacle in OC treatment. Here, the role of miR-4284 in cell sensitivity to paclitaxel in OC was investigated. Two OC cell lines (SKOV3ip1 and HeyA8) were utilized for the establishment of paclitaxel-resistant cell lines. Reverse transcription-quantitative PCR (RT-qPCR) was applied to analyze the levels of miR-4284 and potential mRNAs in OC cell lines. Western blotting was performed to evaluate the levels of DNA meiotic recombinase 1 (DMC1) protein and cell cycle-associated proteins. Identification of the relationship between miR-4284 and DMC1 was achieved by luciferase reporter assay. CCK-8 and flow cytometry assays were utilized for evaluating the impact of miR-4284 on the malignant characteristics of paclitaxel-resistant OC cells. MiR-4284 was upregulated in paclitaxel-resistant OC cell lines and correlated with an adverse prognosis in OC patients. Depletion of miR-4284 suppressed cell proliferation and cell cycle progression of paclitaxel-resistant OC. MiR-4284 targeted DMC1 which was downregulated in paclitaxel-resistant cells and reversed the inhibitory influence of miR-4284 silencing on the malignant characters of paclitaxel-resistant OC cells. MiR-4284 targets DMC1 to suppress sensitivity to paclitaxel in human OC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma* / genetics
  • Cell Cycle Proteins* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins* / genetics
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Paclitaxel / pharmacology

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MIRN4284 microRNA, human
  • MicroRNAs
  • DMC1 protein, human
  • Paclitaxel