Targeted silencing of inhibitors of apoptosis proteins with siRNAs: a potential anti-cancer strategy for hepatocellular carcinoma

Asian Pac J Cancer Prev. 2013;14(9):4943-52. doi: 10.7314/apjcp.2013.14.9.4943.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a very poor prognosis. Despite significant improvements in diagnosis and treatment in recent years, the long-term therapeutic efficacy is poor, partially due to tumor metastasis, recurrence, and resistance to chemo- or radio-therapy. Recently, it was found that a major feature of tumors is a combination of unrestrained cell proliferation and impaired apoptosis. There are now 8 recognized members of the IAP-family: NAIP, c-IAP1, c-IAP2, XIAP, Survivin, Bruce, Livin and ILP-2. These proteins all contribute to inhibition of apoptosis, and provide new potential avenues of cancer treatment. As a powerful tool to suppress gene expression in mammalian cells, RNAi species for inhibiting IAP genes can be directed against cancers. This review will provide a brief introduction to recent developments of the application IAP-siRNA in tumor studies, with the aim of inspiring future treatment of HCC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics
  • Apoptosis*
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / therapy*
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing*
  • Genetic Therapy*
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
  • Inhibitor of Apoptosis Proteins / genetics
  • Liver Neoplasms / genetics
  • Liver Neoplasms / therapy*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neuronal Apoptosis-Inhibitory Protein / antagonists & inhibitors
  • Neuronal Apoptosis-Inhibitory Protein / genetics
  • RNA, Small Interfering / therapeutic use*
  • Survivin
  • Ubiquitin-Protein Ligases
  • X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors
  • X-Linked Inhibitor of Apoptosis Protein / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • BIRC5 protein, human
  • BIRC6 protein, human
  • BIRC7 protein, human
  • BIRC8 protein, human
  • Inhibitor of Apoptosis Proteins
  • NAIP protein, human
  • Neoplasm Proteins
  • Neuronal Apoptosis-Inhibitory Protein
  • RNA, Small Interfering
  • Survivin
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • BIRC2 protein, human
  • BIRC3 protein, human
  • Baculoviral IAP Repeat-Containing 3 Protein
  • Ubiquitin-Protein Ligases