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MiR-129 reduces CDDP resistance in gastric cancer cells by inhibiting MAPK3

H-Y Cao1, C-H Xiao, H-J Lu

  • 1Department of Clinical Laboratory, Affiliated Traditional Chinese Medicine Hospital of Nantong University, Nantong, Jiangsu, China. ppfrrbfbrt@sina.com.

European Review for Medical and Pharmacological Sciences
|August 6, 2019
PubMed
Abstract

Insights

Decreased miR-129 and increased MAPK3 expression correlate with cisplatin resistance in gastric cancer. Restoring miR-129 levels combats drug resistance by inhibiting MAPK3, reducing proliferation, and promoting apoptosis.

Area of Science:

  • Molecular biology
  • Oncology
  • Gene regulation

Background:

  • Mitogen-activated protein kinase 3 (MAPK3) abnormal expression is linked to tumor progression and drug resistance.
  • MicroRNA-129 (miR-129) is implicated in gastric cancer development.
  • Bioinformatics suggests miR-129 targets MAPK3, indicating a potential regulatory relationship.

Purpose of the Study:

  • To investigate miR-129's role in regulating MAPK3 expression in gastric cancer.
  • To determine the effect of miR-129 on gastric cancer cell proliferation, apoptosis, and cisplatin resistance.
  • To explore the therapeutic potential of modulating miR-129/MAPK3 in cisplatin-resistant gastric cancer.

Main Methods:

  • Dual-luciferase reporter gene assay to confirm the miR-129 and MAPK3 interaction.
  • Quantitative analysis of miR-129 and MAPK3 expression in cisplatin-resistant (MGC-803/CDDP) versus parental (MGC-803) gastric cancer cells.
  • In vitro experiments involving miR-129 mimic transfection in MGC-803/CDDP cells, followed by Western blot for MAPK3/p-MAPK3 and flow cytometry for apoptosis and proliferation.

Main Results:

  • A direct targeting relationship between miR-129 and MAPK3 mRNA was confirmed.
  • MGC-803/CDDP cells exhibited significantly lower miR-129 and higher MAPK3 expression compared to MGC-803 cells.
  • Overexpression of miR-129 in MGC-803/CDDP cells led to decreased MAPK3/p-MAPK3, increased apoptosis, and reduced proliferation.

Conclusions:

  • Reduced miR-129 and elevated MAPK3 expression are associated with cisplatin resistance in gastric cancer.
  • Upregulating miR-129 effectively inhibits MAPK3, suppresses proliferation, induces apoptosis, and overcomes cisplatin resistance in gastric cancer cells.

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