Inhibition of microRNA-16 facilitates the paclitaxel resistance by targeting IKBKB via NF-κB signaling pathway in hepatocellular carcinoma

Biochem Biophys Res Commun. 2018 Sep 5;503(2):1035-1041. doi: 10.1016/j.bbrc.2018.06.113. Epub 2018 Aug 2.

Abstract

Hepatocellular carcinoma (HCC) is a common malignant tumor usually resistant to chemotherapy. MicroRNAs play important roles in modulation of carcinogenesis and chemoresistance, which miR-16 has been reported to mediate chemoresistance in many types of cancers. However, the role of miR-16 in HCC remains unknown. The aim of this study was to investigate whether miR-16 is participated in chemoresistance in HCC and shed light on the underlying molecular mechanisms. The findings of the current study discover that miR-16 is down-regulated in HCC tissue and cell lines. The results demonstrate that the inhibition of miR-16 renders resistance to paclitaxel in vitro and in vivo by targeting IKBKB via NF-κB signaling pathway, suggesting that miR-16 may be a meaningful therapeutic potential to overcome drug resistance in HCC.

Keywords: Hepatocellular carcinoma; IKBKB; NF-κB; Paclitaxel resistance; miR-16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • I-kappa B Kinase / genetics*
  • I-kappa B Kinase / metabolism
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • NF-kappa B / metabolism
  • Paclitaxel / pharmacology*
  • Paclitaxel / therapeutic use
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • MIRN16 microRNA, human
  • MicroRNAs
  • Mirn16 microRNA, mouse
  • NF-kappa B
  • I-kappa B Kinase
  • Paclitaxel