miR-135b-5p promotes gastric cancer progression by targeting CMTM3

Mingdong Lu1, Yingpeng Huang1, Weijian Sun2

  • 1Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong, P.R. China.

Insights

MicroRNA-135b-5p promotes gastric cancer progression by inhibiting the tumor suppressor CMTM3. Suppressing miR-135b-5p or overexpressing CMTM3 could be a novel therapeutic strategy for gastric cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) acts as a tumor suppressor gene, inhibiting metastasis and epithelial-mesenchymal transition (EMT) in gastric cancer.
  • The specific role of CMTM3 in gastric cancer cell proliferation and its regulatory mechanisms remain largely undefined.

Purpose of the Study:

  • To investigate the regulatory relationship between CMTM3 and miR-135b-5p in gastric cancer.
  • To elucidate the functional impact of CMTM3 and miR-135b-5p on gastric cancer cell proliferation, invasion, and apoptosis.
  • To validate the therapeutic potential of targeting this pathway in vivo.

Main Methods:

  • Quantitative real-time PCR (RT-qPCR) and immunohistochemistry (IHC) to assess gene expression.
  • Dual-luciferase reporter assay to confirm direct targeting.
  • In vitro assays including CCK8, Transwell, and flow cytometry.
  • In vivo studies using a BALB/c nude mouse xenograft model.

Main Results:

  • miR-135b-5p expression was negatively correlated with CMTM3 expression in gastric cancer tissues.
  • miR-135b-5p directly targets and inhibits CMTM3 in gastric cancer cells.
  • Overexpression of CMTM3 or inhibition of miR-135b-5p suppressed cancer cell proliferation, invasion, and cell cycle progression, while promoting apoptosis.
  • In vivo, miR-135b-5p inhibition significantly reduced tumor growth and increased CMTM3 expression.

Conclusions:

  • The miR-135b-5p/CMTM3 axis plays a critical role in regulating gastric cancer progression and metastasis.
  • Overexpression of miR-135b-5p promotes gastric cancer by suppressing CMTM3.
  • Targeting the miR-135b-5p/CMTM3 pathway offers a promising therapeutic strategy for gastric cancer treatment.

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