[Mechanism of miR-200b-3p-induced FOSL2 inhibitorion of endometrial cancer cell proliferation and metastasis]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2024 Dec;40(12):1089-1095.
[Article in Chinese]

Abstract

Objective The purpose of this study was to investigate how miR-200b-3p inhibitors the proliferation and metastasis of endometrial cancer(EC) cells by inducing the expression of FOS-like antigen 2(FOSL2) of activator protein 1(AP1) transcription family. Methods Endometrial cancer cell line HEC-1-A was divided into 12 groups: NC-mimic (transfected with negative control NC mimic), miR-200b-3p mimic (transfected with miR-200b-3p mimic), NC-inhibitor (transfected with negative control NC inhibitor), miR-200b-3p inhibitor group (transfected with miR-200b-3p inhibitor), si-NC (transfected with negative control Si-NC), si-FOSL2 (transfected with si-FOSL2), oe-NC (transfected with negative control oe-NC), oe-FOSL2 group (oe-FOSL2), miR-200b-3p mimic+oe-NC group (co-transfected with miR-200b-3p mimic and oe-NC), miR-200b-3p mimic+oe-FOSL2 group (co-transfected with miR-200b-3p mimic and oe-FOSL2), miR-200b-3p inhibitor+si-NC group (co-transfected with miR-200b-3p inhibitor and si-NC), miR-200b-3p inhibitor+si-FOSL2 group (co-transfected with miR-200b-3p inhibitor and si-FOSL2). Real-time fluorescence quantitative PCR, Western blot, CCK-8 assay, scratch test and Transwell assay were used to detect the expression of miR-200b-3p mRNA, FOSL2 mRNA and protein expression level, cell proliferation, migration and invasion. Results In endometrial cancer cell lines, the expression of miR-200b-3p was significantly down-regulated, while the expression of FOSL2 was significantly up-regulated. Compared with NC-mimic group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic group was significantly decreased, and the expression of E-cadherin was significantly increased. The cell proliferation, migration rate and the number of transmembrane cells were significantly decreased. Compared with the miR-200b-3p mimic+oe-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic+oe-FOSL2 group was significantly increased, and the expression level of E-cadherin was significantly decreased, and the cell proliferation, migration rate and the number of transmembrane cells were significantly increased. Compared with NC-inhibitor group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibitor group was significantly increased, and the expression of E-cadherin was significantly decreased. The cell proliferation, migration rate and the number of transmembrane cells were significantly increased. Compared with the miR-200b-3p inhibitor+si-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibitor+si-FOSL2 group was significantly decreased, and the expression of E-cadherin was significantly increased; the cell proliferation, migration rate and the number of transmembrane cells were significantly decreased. Conclusion The expression of miR-200b-3p in endometrial cancer cells is down-regulated, which can inhibitor the proliferation, migration and invasion of endometrial cancer cells by regulating the EMT process, and its mechanism is related to its targeted negative regulation of FOSL2 expression.

Publication types

  • English Abstract

MeSH terms

  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation* / drug effects
  • Cell Proliferation* / genetics
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / metabolism
  • Endometrial Neoplasms* / pathology
  • Female
  • Fos-Related Antigen-2* / genetics
  • Fos-Related Antigen-2* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Neoplasm Metastasis* / genetics

Substances

  • MicroRNAs
  • MIRN200 microRNA, human
  • Fos-Related Antigen-2
  • FOSL2 protein, human
  • Cadherins