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MicroRNA-29c-5p suppresses gallbladder carcinoma progression by directly targeting CPEB4 and inhibiting the MAPK

Yi-Jun Shu1,2, Run-Fa Bao1,2, Lin Jiang1,2

  • 1Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.

Cell Death and Differentiation
|January 7, 2017
PubMed

Insights

MicroRNA miR-29c-5p is downregulated in gallbladder cancer (GBC), correlating with poor prognosis. Restoring miR-29c-5p inhibits GBC growth and metastasis by targeting CPEB4.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gallbladder cancer (GBC) presents a poor prognosis with a 5-year survival rate of approximately 5%.
  • MicroRNAs (miRNAs) play a critical role in cancer metastasis, necessitating investigation into their function in GBC.
  • The metastasis-associated miRNA miR-29c-5p's role in GBC requires detailed analysis.

Purpose of the Study:

  • To investigate the expression and functional role of miR-29c-5p in gallbladder cancer.
  • To elucidate the molecular mechanisms underlying miR-29c-5p's function in GBC progression.
  • To evaluate miR-29c-5p as a potential prognostic biomarker and therapeutic target for GBC.

Main Methods:

  • Expression analysis of miR-29c-5p in GBC tissues and correlation with clinical parameters.
  • In vitro studies involving ectopic overexpression of miR-29c-5p to assess its effects on GBC cell proliferation, apoptosis, and metastasis.
  • In vivo tumorigenicity assays and mechanistic studies involving the MAPK pathway and CPEB4 target validation.

Main Results:

  • miR-29c-5p expression was significantly downregulated in GBC and associated with lymph node metastasis, overall survival, and disease-free survival.
  • Overexpression of miR-29c-5p suppressed GBC cell proliferation, metastasis, and colony formation, while inducing apoptosis in vitro and inhibiting tumorigenicity in vivo via the MAPK pathway.
  • Cytoplasmic polyadenylation element binding protein 4 (CPEB4) was identified as a direct target of miR-29c-5p; its restoration reversed the tumor-suppressive effects of miR-29c-5p.

Conclusions:

  • The TGF-β/miR-29c-5p/CPEB4 axis is crucial in GBC pathogenesis and prognosis.
  • miR-29c-5p acts as a tumor-suppressive miRNA in GBC.
  • miR-29c-5p holds potential as a prognostic biomarker and therapeutic target for GBC.

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