miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1

Biomed Pharmacother. 2016 Dec:84:123-129. doi: 10.1016/j.biopha.2016.09.027. Epub 2016 Sep 16.

Abstract

Background: Non-small cell lung cancer (NSCLC) chemoresistance usually limits the clinical efficacy of chemotherapeutic approaches. However, few reports have revealed the regulation of miR-135b and Frizzled-1 (FZD1) involved in NSCLC chemoresistance.

Methods: To identify the mechanism of miR-135b and FZD1 in NSCLC chemoresistance and to observe their biological functions, we detected the expression levels of miR-135b and FZD1 by conducting quantitative real-time polymerase chain reaction (RT-qPCR) and modified the expressions of miR-135b and FZD1 by transiently transfecting cells with miR-135b mimics or FZD1-siRNA. The 3'-untranslated region (3'-UTR) of FZD1 combined with miR-135b was verified through dual-luciferase reporter assay.

Results: Compared with that in A549 parental cell lines, the miR-135b expression in drug-resistant lung cancer cell lines (A549/DDP) was decreased and their FZD1 expression was increased. The increased miR-135b expression and silenced FZD1 expression enhanced the sensitivity of resistant cells to cisplatin treatment. The high expression of miR-135b in A549/DDP cells remarkably decreased the mRNA levels of FZD1. FZD1 was further identified as the functional downstream target of miR-135b by directly targeting the 3'-UTR of FZD1.

Conclusion: The amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.

Keywords: Chemoresistance; FZD1; NSCLC; miR-135b.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Down-Regulation / drug effects
  • Down-Regulation / physiology*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / physiology*
  • Frizzled Receptors / antagonists & inhibitors
  • Frizzled Receptors / biosynthesis*
  • Frizzled Receptors / genetics
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics

Substances

  • Antineoplastic Agents
  • FZD1 protein, human
  • Frizzled Receptors
  • MIRN135 microRNA, human
  • MicroRNAs