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MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the

Xizhe Li1, Jiali Zhu2, Yuanqi Liu1

  • 1Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, China.

Cancer Science
|April 8, 2019
PubMed

Insights

MicroRNA-331-3p is downregulated in non-small-cell lung cancer (NSCLC), suppressing tumor cell migration and metastasis. This microRNA targets ErbB2 and VAV2, impacting the Rac1/PAK1/β-catenin pathway and serving as a prognostic marker for NSCLC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs regulate non-small-cell lung cancer (NSCLC) development.
  • The specific role of microRNA (miR)-331-3p in NSCLC remains largely undetermined.
  • Understanding miR-331-3p's function is crucial for identifying novel therapeutic targets and prognostic markers in NSCLC.

Purpose of the Study:

  • To investigate the expression levels and clinical significance of miR-331-3p in NSCLC.
  • To elucidate the role of miR-331-3p in regulating NSCLC cell epithelial-mesenchymal transition (EMT), migration, and metastasis.
  • To identify the direct targets and downstream pathways modulated by miR-331-3p in NSCLC.

Main Methods:

  • Quantitative RT-PCR to assess miR-331-3p expression in NSCLC tissues.
  • In vitro and in vivo assays to evaluate the effects of miR-331-3p on cell migration and metastasis.
  • Luciferase reporter assays, Western blot, and immunohistochemistry to identify direct targets.
  • Immunofluorescence, immunoprecipitation, and Rac1 activity assays to determine the downstream pathway.

Main Results:

  • miR-331-3p was significantly downregulated in NSCLC tissues and correlated with clinicopathological characteristics.
  • Downregulation of miR-331-3p was associated with poorer prognosis, identifying it as an independent prognostic marker.
  • miR-331-3p suppressed EMT, migration, and metastasis of NSCLC cells both in vitro and in vivo.
  • ErbB2 and VAV2 were identified as direct targets of miR-331-3p.
  • miR-331-3p regulated the activities of Rac1, PAK1, and β-catenin through targeting ErbB2 and VAV2.

Conclusions:

  • miR-331-3p acts as a tumor suppressor in NSCLC by inhibiting EMT, migration, and metastasis.
  • The tumor-suppressive function of miR-331-3p is mediated through the targeting of ErbB2 and VAV2, subsequently affecting the Rac1/PAK1/β-catenin signaling axis.
  • miR-331-3p holds potential as a valuable prognostic biomarker for NSCLC patients.
Keywords:
ErbB2Rac1VAV2microRNAnon-small-cell lung cancer

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