Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma

Karagonlar Z. F., Korhan P., Atabey N.

DRUG DEVELOPMENT RESEARCH, vol.76, no.7, pp.357-367, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 76 Issue: 7
  • Publication Date: 2015
  • Doi Number: 10.1002/ddr.21274
  • Journal Name: DRUG DEVELOPMENT RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.357-367
  • Keywords: c-Met, hepatocyte growth factor, miRNA, hepatocellular carcinoma, targeted therapy, HEPATOCYTE GROWTH-FACTOR, RECEPTOR TYROSINE KINASE, TUMOR-SUPPRESSOR FUNCTIONS, CELL-PROLIFERATION, INHIBITS MIGRATION, DOXORUBICIN SENSITIVITY, MESENCHYMAL TRANSITION, EXPRESSION SIGNATURE, LIVER, METASTASIS
  • Dokuz Eylül University Affiliated: Yes

Abstract

Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. Drug Dev Res 76 : 357-367, 2015. (c) 2015 Wiley Periodicals, Inc.