Integrated transcriptomic and proteomic analyses reveal ɑ-lipoic acid-regulated cell proliferation via Grb2-mediated signalling in hepatic cancer cells

Lan Yang, Xiliang Wang, Juan Xu, Ya Wen, Manqiao Zhang, Jingxiao Lu, Rongfu Wang, Xiaojuan Sun

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Hepatocellular carcinoma is the most frequent primary liver cancer worldwide. The use of antioxidants as cancer prevention and treatment agents has become a focus of research in recent years due to their limited adverse effects. Alpha lipoic acid (ɑ-LA) is synthesized in the liver and is considered a naturally occurring antioxidant. In this study, a total of 4446 differentially expressed genes (2097 down-regulated and 2349 up-regulated) were identified via RNA-Seq in HepG2 cells after exposure to α-LA for 24 hrs. Moreover, GO and KEGG pathway analyses showed that cancer-relevant cell membrane proteins were significantly affected. An interaction network analysis predicted that Grb2 might mediate the key target pathways activated by exposure to ɑ-LA. Verification of the RNA-Seq and iTRAQ results confirmed that Grb2 mediated the ɑ-LA-induced inhibition of cell proliferation in vitro. Furthermore, the analysis of human hepatocellular carcinoma specimens obtained from the GEO database showed that the expression of EGFR and Met correlated with that of Grb2. These findings provide a novel mechanism through which ɑ-LA regulates cell proliferation via the down-regulation of growth factor-stimulated Grb2 signalling.

Original languageEnglish (US)
Pages (from-to)2981-2992
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume22
Issue number6
DOIs
StatePublished - Jun 2018

Keywords

  • Grb2
  • RNA-Seq
  • hepatocellular carcinomas
  • proteome
  • ɑ-lipoic acid

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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