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MiR-203 over-expression promotes prostate cancer cell apoptosis and reduces ADM resistance

L-Z Chen1, Z Ding, Y Zhang

  • 1Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. wangxinghuan@whu.edu.cn.

European Review for Medical and Pharmacological Sciences
|June 28, 2018
PubMed
Abstract

Insights

MicroRNA 203 (miR-203) targets and inhibits MEK1, suppressing prostate cancer cell proliferation and drug resistance. Increasing miR-203 levels may offer a therapeutic strategy for prostate cancer by reducing MEK1 expression and the ERK/MAPK pathway.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • The ERK/MAPK signaling pathway regulates cell proliferation, apoptosis, and drug resistance.
  • Down-regulation of microRNA 203 (miR-203) is linked to prostate cancer.
  • MEK1 is an upstream activator of the ERK/MAPK pathway.

Purpose of the Study:

  • To investigate the role of miR-203 in regulating prostate cancer cell proliferation, apoptosis, and adriamycin (ADM) resistance.
  • To explore the mechanism by which miR-203 affects MEK1 expression.
  • To determine the impact of miR-203 on the ERK/MAPK signaling pathway and Bcl-2 expression in prostate cancer.

Main Methods:

  • Dual luciferase assay to confirm the miR-203 and MEK1 interaction.
  • Comparison of miR-203, MEK1, p-ERK1/2, and Bcl-2 expression in normal and prostate cancer cells (including drug-resistant cells).
  • Flow cytometry to assess apoptosis and proliferation in response to ADM treatment and miR-203 mimic/si-MEK1 transfection.

Main Results:

  • miR-203 directly targets and inhibits MEK1 expression.
  • Prostate cancer cells (PC-3M/ADM) exhibited lower miR-203 and apoptosis, but higher MEK1, p-ERK1/2, Bcl-2, and proliferation compared to PC-3M cells.
  • Transfection with miR-203 mimic and/or si-MEK1 reduced MEK1, p-ERK1/2, and Bcl-2, decreased proliferation, induced apoptosis, and lowered drug resistance.

Conclusions:

  • miR-203 elevation suppresses prostate cancer cell proliferation and ADM resistance.
  • This suppression is achieved by targeting MEK1, thereby inhibiting the ERK/MAPK signaling pathway and reducing Bcl-2 expression.
  • miR-203 acts as a tumor suppressor in prostate cancer, offering potential therapeutic implications.

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