RNA interference against granulin-epithelin precursor prevents hepatocellular carcinoma growth: Its application as a therapeutic agent

  • Authors: Mi-Young Park, Yoon Shin Park, Jae-Hwan Nam
  • View Affiliations

  • Published online on: Wednesday, June 22, 2011
  • Pages: 853-861
  • DOI: 10.3892/ijo.2011.1095

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. However, little is known regarding the molecular mechanism of HCC development and progression and effective therapeutic methods. Recently, the granulin-epithelin precursor (GEP) was reported as a novel growth factor that can control HCC cell proliferation. Using the CAPSID program, we designed three small interfering RNAs (siRNAs) targeting the GEP gene (GEP-siRNA1, 2 and 3) and examined their tumor regression and suppression effects on cell proliferation. GEP-siRNA1 exhibited the strongest anti-proliferative effect among the GEP-siRNAs, in a time-dependent manner. To increase the biostability of the siRNA, we also constructed a short hairpin RNA (shRNA) using an H1/TO promoter with the same sequence of GEP-siRNA1 (GEP-shRNA). GEP-shRNA decreased the expression levels of GEP and tumor cell growth via cell cycle arrest at the G2/M stage and down-regulation of the cell proliferation proteins cyclin D1 and α-tubulin. Furthermore, GEP-shRNA inhibited tumor growth significantly after intratumoral injection into tumor-bearing Balb/C nude mice. Taken together, these results represent the first therapeutic application of RNA interference to GEP, which is a promising target molecule for HCC treatment, as an approach for the suppression of HCC cell proliferation.
Journal Cover

October 2011
Volume 39 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.657
Ranked #31/196 Oncology
(total number of cites)

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APA
Park, M., Park, Y., & Nam, J. (2011). RNA interference against granulin-epithelin precursor prevents hepatocellular carcinoma growth: Its application as a therapeutic agent. International Journal of Oncology, 39(4), 853-861.
MLA
Park, Park, and Jae-Hwan Nam. "RNA interference against granulin-epithelin precursor prevents hepatocellular carcinoma growth: Its application as a therapeutic agent." International Journal of Oncology International Journal of Oncology 39.4 (2011): 853-861.
Chicago
Park, Park, and Jae-Hwan Nam. "RNA interference against granulin-epithelin precursor prevents hepatocellular carcinoma growth: Its application as a therapeutic agent." International Journal of Oncology International Journal of Oncology 39 no. 4 (2011): 853-861.