TSPAN12 promotes chemoresistance and proliferation of SCLC under the regulation of miR-495

Biochem Biophys Res Commun. 2017 Apr 29;486(2):349-356. doi: 10.1016/j.bbrc.2017.03.044. Epub 2017 Mar 14.

Abstract

Studies have shown that TSPAN12 serves as an oncogenic gene or tumor suppressor depending on the types of cancer. However, its role in the drug resistance of small cell lung cancer (SCLC) is still unknown. In this study, we investigated whether TSPAN12 regulates chemoresistance, proliferation and tumor growth of SCLC under the regulation of miR-495 using two drug resistant cell lines. The results showed that down-regulation of TSPAN12 inhibited cells chemoresistance, proliferation and tumor growth. Besides, TSPAN12 elevation in SCLC specimens correlated with poor pathologic stage and shorter survival time. In addition, the dual luciferase assay indicated that TSPAN12 was one of the directly targeted genes of miR-495. Our study revealed that TSPAN12 promoted chemoresistance of SCLC under the regulation of miR-495. TSPAN12 depletion is a promising strategy for inhibiting the chemoresistance in SCLC.

Keywords: Chemoresistance; SCLC; TSPAN12; miR-495.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology
  • Survival Analysis
  • Tetraspanins / antagonists & inhibitors
  • Tetraspanins / genetics*
  • Tetraspanins / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • MIRN495 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • TSPAN12 protein, human
  • Tetraspanins
  • Luciferases
  • Cisplatin