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LncRNA-MEG3 inhibits cell proliferation and invasion by modulating Bmi1/RNF2 in cholangiocarcinoma

Jinglin Li1, Xingming Jiang1, Chunlong Li1

  • 1Department of HPB Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

Journal of Cellular Physiology
|May 24, 2019
PubMed

Insights

Maternally expressed gene 3 (MEG3) is downregulated in cholangiocarcinoma (CCA), a bile duct cancer. Restoring MEG3 suppresses CCA growth and metastasis, suggesting it's a potential therapeutic target.

Area of Science:

  • Molecular Oncology
  • Cancer Biology
  • Long Noncoding RNAs

Background:

  • Cholangiocarcinoma (CCA) incidence is rising globally, with limited effective treatments.
  • Maternally expressed gene 3 (MEG3), a long noncoding RNA (lncRNA), plays roles in digestive system tumors.
  • The clinical significance and function of MEG3 in CCA are not well understood.

Purpose of the Study:

  • To investigate the clinical relevance and biological function of MEG3 in cholangiocarcinoma.
  • To explore MEG3's potential as a diagnostic marker and therapeutic target for CCA.

Main Methods:

  • Analysis of MEG3 expression levels in CCA tissues and cell lines.
  • Correlation of MEG3 expression with clinical parameters (TNM stage, lymph node invasion, survival).
  • In vitro and in vivo functional assays to assess the impact of MEG3 overexpression or knockdown on CCA cell behavior.
  • Investigation of MEG3's interaction with B lymphoma Mo-MLV insertion region 1 (Bmi1) and polycomb repressive complex 1.

Main Results:

  • MEG3 expression was significantly downregulated in CCA tissues and cells compared to controls.
  • Reduced MEG3 expression correlated with advanced TNM stage, lymph node invasion, and poorer patient survival.
  • MEG3 overexpression inhibited CCA cell proliferation, migration, and invasion by reversing epithelial-mesenchymal transition (EMT).
  • MEG3 knockdown promoted proliferation, metastasis, and EMT, effects partially mediated by Bmi1.

Conclusions:

  • MEG3 acts as a tumor suppressor in cholangiocarcinoma.
  • Downregulation of MEG3 is an independent predictor of poor prognosis in CCA patients.
  • MEG3 exerts its function partly through the Bmi1-mediated polycomb repressive complex 1 pathway.
  • MEG3 holds promise as a diagnostic indicator and therapeutic target for CCA.
Keywords:
MEG3cholangiocarcinomalncRNAtumor suppressor

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