microRNA-338-3p functions as a tumor suppressor in human non‑small‑cell lung carcinoma and targets Ras-related protein 14

Mol Med Rep. 2015 Feb;11(2):1400-6. doi: 10.3892/mmr.2014.2880. Epub 2014 Nov 6.

Abstract

microRNAs (miRNAs) have been demonstrated to be important gene regulators with critical roles in diverse biological processes, including tumorigenesis. Accumulating evidence suggests that miR‑338-3p exerts a tumor suppressor role and is downregulated in tumors, including gastric cancer and colorectal carcinoma. However, the role of miR‑338-3p in lung cancer, particularly non‑small‑cell lung carcinoma (NSCLC), has remained elusive. In the present study, the expression levels of miR‑338-3p in NSCLC tissues were compared with those of matched normal tissues by use of polymerase chain reaction analysis. miR-338-3p was shown to be downregulated in NSCLC tissues, and the expression levels of miR‑338‑3p were significantly correlated with NSCLC cancer differentiation, pathological stage and lymph‑node metastasis. Ectopic miR-338-3p expression significantly suppressed the in vitro proliferation and colony formation of NSCLC cells and enhanced apoptosis. Of note, ectopic miR‑338-3p expression significantly inhibited Ras‑related protein 14 (RAB14) mRNA and protein expression, and reduced luciferase reporter activity containing the RAB14 3'-untranslated region through the first binding site. These findings suggested that miR‑338-3p regulated the survival of NSCLC cells partially through the downregulation of RAB14. Therefore, targeting the miR‑338-3p/RAB14 interaction may serve as a novel therapeutic application to treat NSCLC patients.

MeSH terms

  • 3' Untranslated Regions
  • Aged
  • Apoptosis
  • Base Sequence
  • Binding Sites
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • RNA, Messenger / metabolism
  • Sequence Alignment
  • Transfection
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • 3' Untranslated Regions
  • MIRN338 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Rab14 protein, human
  • rab GTP-Binding Proteins