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miR-378a-3p sensitizes ovarian cancer cells to cisplatin through targeting MAPK1/GRB2

Zhi-Hong Xu1, Tie-Zhu Yao2, Wei Liu1

  • 1Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province 050011, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|September 28, 2018
PubMed

Insights

MicroRNA-378a-3p (miR-378a-3p) is downregulated in ovarian cancer, suppressing tumor growth. Restoring miR-378a-3p enhances chemosensitivity to cisplatin by targeting MAPK1 and GRB2.

Area of Science:

  • Gynecologic Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Ovarian cancer is a leading gynecological tumor with significant chemoresistance challenges.
  • MicroRNAs (miRNAs) show anti-oncogenic potential, with miR-378a-3p previously noted for sensitizing breast cancer cells to chemotherapy.

Purpose of the Study:

  • To investigate the potential of miR-378a-3p as a chemosensitizer in ovarian cancer.
  • To explore the underlying molecular mechanisms of miR-378a-3p's function in ovarian cancer.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and northern blot analysis to assess miR-378a-3p expression.
  • Kaplan-Meier analysis for prognosis correlation.
  • Gain-of-function assays and rescue experiments to evaluate functional roles.
  • Mechanism investigations to identify molecular targets.

Main Results:

  • miR-378a-3p was significantly downregulated in ovarian cancer tissues and cell lines.
  • Low miR-378a-3p expression correlated with poor patient prognosis.
  • Overexpression of miR-378a-3p inhibited cell proliferation, promoted apoptosis, and enhanced cisplatin sensitivity.
  • MAPK1 and GRB2 were identified as direct targets of miR-378a-3p, mediating its effects.

Conclusions:

  • miR-378a-3p acts as a tumor suppressor in ovarian cancer.
  • miR-378a-3p enhances ovarian cancer cell sensitivity to cisplatin by targeting MAPK1 and GRB2.
  • miR-378a-3p represents a potential therapeutic strategy for overcoming chemoresistance in ovarian cancer.
Keywords:
CisplatinGRB2MAPK1Ovarian cancermiR-378a-3p

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