Molecular pathways and functional analysis of miRNA expression associated with paclitaxel-induced apoptosis in hepatocellular carcinoma cells

Pharmacology. 2013;92(3-4):167-74. doi: 10.1159/000354585. Epub 2013 Sep 20.

Abstract

Background: We postulated that microRNAs (miRNAs) might be involved in hepatocellular carcinoma (HCC) targeted chemotherapy with paclitaxel. This study sought to generate a list of potential miRNA-based biomarkers and their potential targets to better understand the response to paclitaxel treatment in HCC.

Methods: Cell viability proliferation assays were conducted to test the sensitivity of the HepG2 cells to paclitaxel. The morphological changes of apoptosis were assessed with 4',6-diamidino-2-phenylindole staining. Differential expression patterns of miRNA in the HepG2 cells either treated or not treated were analyzed using miRNA microarrays.

Results: The array experiments have identified 54 miRNAs whose basal expression levels differed by >2-fold and p < 0.05 between the two phenotypic groups. The data were validated by a quantitative real-time PCR of 8 selected miRNAs (miR-21, miR-1274a, miR-1260, miR-1290, miR-508-5p, miR-877, miR-1246, miR-183*). The PI3K/Akt, mitogen-activated protein kinase (MAPK), TGF-β, ErbB, p53, cell cycle, mammalian target of rapamycin, and Jak-STAT signaling pathways were involved in paclitaxel-induced apoptosis.

Conclusions: The manipulation of one or more of these miRNAs could be an important approach for the improved management of paclitaxel therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Cell Proliferation / drug effects
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • MicroRNAs / genetics*
  • Microarray Analysis
  • Paclitaxel / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • MicroRNAs
  • Paclitaxel