miR-195 potentiates the efficacy of microtubule-targeting agents in non-small cell lung cancer

Xiaojie Yu, Yiqiang Zhang, Xiuye Ma, Alexander Pertsemlidis

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Microtubule-targeting agents (MTAs) are widely used for the treatment of non-small cell lung cancer (NSCLC). The response rate is only ∼25%, mainly attributable to drug resistance. To identify determinants of resistance in NSCLC, we performed a high-throughput screen using a library of miRNA mimics. Here we report that miR-195 synergizes with MTAs to inhibit the growth of NSCLC cells in vitro, that increased expression of miR-195 sensitizes NSCLC cells to MTAs and that repression of miR-195 confers resistance to MTAs. We show that NSCLC tumors over-expressing miR-195 are more sensitive to MTA treatment and that induced expression of miR-195 in NSCLC tumors potentiates the anti-tumor effect of MTAs. Additionally, we demonstrate that miR-195 targets checkpoint kinase 1 (CHEK1) to regulate the response of NSCLC cells to MTAs, that over-expression of CHEK1 contributes to resistance to MTAs and that knock-down of CHEK1 synergizes with MTAs to repress cell growth. Our results highlight the importance of miR-195 in regulating the response of NSCLC cells to MTAs and underline the potential application of miR-195 as a biomarker for response to MTAs, and as a therapeutic adjuvant to MTA treatment.

Original languageEnglish (US)
Pages (from-to)85-93
Number of pages9
JournalCancer Letters
Volume427
DOIs
StatePublished - Jul 28 2018

Keywords

  • CHEK1
  • Eribulin
  • Non-small cell lung cancer
  • Paclitaxel
  • miR-195

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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