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MicroRNA-30a-5p inhibits gallbladder cancer cell proliferation, migration and metastasis by targeting E2F7

Yuan-Yuan Ye1,2,3, Jia-Wei Mei1,2,3, Shan-Shan Xiang1,2,3

  • 1Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.

Cell Death & Disease
|March 16, 2018
PubMed

Insights

MicroRNA-30a-5p (miR-30a-5p) acts as a tumor suppressor in gallbladder carcinoma (GBC). Lower miR-30a-5p levels correlate with poorer survival and increased metastasis, suggesting its therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gallbladder carcinoma (GBC) is an aggressive bile duct cancer with poor prognosis.
  • MicroRNA-30a-5p (miR-30a-5p) is a known tumor suppressor in various cancers.
  • The specific role and mechanism of miR-30a-5p in GBC remain unclear.

Purpose of the Study:

  • To investigate the role of miR-30a-5p in the development and progression of GBC.
  • To elucidate the underlying molecular mechanisms of miR-30a-5p action in GBC.
  • To evaluate miR-30a-5p as a potential prognostic biomarker and therapeutic target for GBC.

Main Methods:

  • Analysis of miR-30a-5p expression in GBC tissues and adjacent non-tumour tissues (NATs) from 42 patients.
  • In vitro studies involving GBC cell lines (GBC-SD, NOZ) to assess the effects of miR-30a-5p inhibition/mimicry on cell proliferation, migration, and invasion.
  • In vivo experiments using nude mice to evaluate tumor growth and metastasis.
  • Dual luciferase reporter assays to identify direct targets of miR-30a-5p.

Main Results:

  • Decreased miR-30a-5p expression was observed in GBC primary lesions compared to NATs.
  • Lower miR-30a-5p levels were significantly associated with shorter disease-free survival (DFS) and overall survival (OS).
  • miR-30a-5p inhibition promoted GBC cell proliferation, migration, invasion, and β-catenin nuclear translocation, while miR-30a-5p mimics had opposite effects.
  • In vivo, miR-30a-5p overexpression reduced tumor growth and hepatic metastasis.
  • E2F transcription factor 7 (E2F7) was identified as a direct target of miR-30a-5p, and it antagonized miR-30a-5p's suppressive effects.

Conclusions:

  • MiR-30a-5p functions as a tumor suppressor in GBC by attenuating epithelial-mesenchymal transition (EMT) and metastasis.
  • The mechanism involves targeting E2F7, thereby inhibiting GBC cell proliferation and metastasis.
  • MiR-30a-5p holds promise as a novel prognostic biomarker and a potential molecular therapeutic target for GBC.

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