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MicroRNA-137-mediated Src oncogenic signaling promotes cancer progression

Rie Kokuda1, Risayo Watanabe2, Daisuke Okuzaki3

  • 1Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|July 3, 2018
PubMed

Insights

Down-regulation of microRNA-137 (miR-137) promotes colon cancer progression by upregulating tyrosine kinase c-Src. Restoring miR-137 suppresses tumor growth and invasion, highlighting a novel mechanism in cancer.

Area of Science:

  • Molecular Oncology
  • Cancer Biology
  • MicroRNA Therapeutics

Background:

  • The tyrosine kinase c-Src is overexpressed and activated in many human cancers.
  • The molecular mechanisms driving c-Src upregulation in cancer remain largely unknown.
  • MicroRNAs (miRNAs) are implicated in cancer progression and can regulate gene expression.

Purpose of the Study:

  • To investigate if microRNA-mediated upregulation of c-Src promotes cancer progression.
  • To identify specific miRNAs that interact with the 3'-untranslated region (3'-UTR) of c-Src mRNA.
  • To elucidate the role of miR-137 in colon cancer development and metastasis.

Main Methods:

  • Screening of miRNAs with complementarity to the c-Src mRNA 3'-UTR.
  • Analysis of miR-137 expression in human colon cancer cells and tissues.
  • Functional assays including tumor growth, cell adhesion, invasion, and focal contact disruption.
  • Restoration of c-Src expression in miR-137-treated cells.
  • Identification of miR-137 targets, including AKT2 and paxillin.

Main Results:

  • Down-regulation of miR-137 was significantly associated with c-Src-mediated colon cancer progression.
  • Re-expression of miR-137 suppressed tumor growth, cell adhesion, and invasion.
  • miR-137 targets AKT2 and paxillin, and its regulation of c-Src/AKT2/paxillin is crucial for tumor growth and malignancy.
  • miR-137 suppressed Src-related oncogenic signaling and modulated downstream miRNA expression.

Conclusions:

  • miR-137 plays a critical tumor-suppressive role in colon cancer by regulating c-Src, AKT2, and paxillin.
  • The miR-137/c-Src/AKT2/paxillin pathway is essential for controlling tumor growth and malignancy.
  • Dysfunction of this novel regulatory mechanism may trigger tumor progression in various human cancers with c-Src upregulation.
Keywords:
AKT2Srccolon cancermalignancymiR-137paxillintumor growth

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