MicroRNA-26a promotes anoikis in human hepatocellular carcinoma cells by targeting alpha5 integrin

Xiang Zhang, Shu-Li Cheng, Ka Bian, Lei Wang, Xiao Zhang, Bo Yan, Lin-Tao Jia, Jing Zhao, Noor Gammoh, An-Gang Yang, Rui Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Metastasis is the major reason for the death of patients suffering from malignant diseases such as human hepatocellular carcinoma (HCC). Among the complex metastatic process, resistance to anoikis is one of the most important steps. Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins. However, whether miR-26a can also influence anoikis has not been well established. Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo. With a combinational analysis of bioinformatics and public clinical databases, we predicted that alpha5 integrin (ITGA5), an integrin family member, is a putative target of miR-26a. Furthermore, we provide experimental evidence to confirm that ITGA5 is a bona fide target of miR-26a. Through gain- and loss-of-function studies, we demonstrate that ITGA5 is a functional target of miR-26a-induced anoikis in HCC cells. Collectively, our findings reveal that miR-26a is a novel player during anoikis and a potential therapeutic target for the treatment of metastatic HCC.

Original languageEnglish
Pages (from-to)2277-89
Number of pages13
JournalOncotarget
Volume6
Issue number4
Early online date10 Dec 2014
DOIs
Publication statusPublished - 10 Feb 2015

Keywords

  • Animals
  • Anoikis
  • Carcinoma, Hepatocellular
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Integrin alpha5
  • Liver Neoplasms
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins c-akt
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Heterologous

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