Oncotarget

Research Papers:

MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in liver carcinogenesis

Iryna Kindrat _, Volodymyr Tryndyak, Aline de Conti, Svitlana Shpyleva, Thilak K. Mudalige, Tetyana Kobets, Anna M. Erstenyuk, Frederick A. Beland and Igor P. Pogribny

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Oncotarget. 2016; 7:1276-1287. https://doi.org/10.18632/oncotarget.6004

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Abstract

Iryna Kindrat1,3, Volodymyr Tryndyak1, Aline de Conti1, Svitlana Shpyleva1, Thilak K. Mudalige2, Tetyana Kobets1, Anna M. Erstenyuk3, Frederick A. Beland1, Igor P. Pogribny1

1Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA

2Office of Regulatory Affairs, Arkansas Regional Laboratory, U.S. Food and Drug Administration, Jefferson, AR, USA

3Department of Biological and Medical Chemistry, Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine

Correspondence to:

Igor P. Pogribny, e-mail: igor.pogribny@fda.hhs.gov

Keywords: hepatocellular carcinoma, iron metabolism, transferrin receptor 1, microRNA-152, dysregulation

Received: September 22, 2015     Accepted: October 06, 2015     Published: October 19, 2015

ABSTRACT

Over-expression of transferrin receptor 1 (TFRC) is observed in hepatocellular carcinoma (HCC); however, there is a lack of conclusive information regarding the mechanisms of this dysregulation. In the present study, we demonstrated a significant increase in the levels of TFRC mRNA and protein in preneoplastic livers from relevant experimental models of human hepatocarcinogenesis and in human HCC cells. Additionally, using the TCGA database, we demonstrated an over-expression of TFRC in human HCC tissue samples and a markedly decreased level of microRNA-152 (miR-152) when compared to non-tumor liver tissue. The results indicated that the increase in levels of TFRC in human HCC cells and human HCC tissue samples may be attributed, in part, to a post-transcriptional mechanism mediated by a down-regulation of miR-152. This was evidenced by a strong inverse correlation between the level of TFRC and the expression of miR-152 in human HCC cells (r = −0.99, p = 4. 7 × 10−9), and was confirmed by in vitro experiments showing that transfection of human HCC cell lines with miR-152 effectively suppressed TFRC expression. This suggests that miR-152-specific targeting of TFRC may provide a selective anticancer therapeutic approach for the treatment of HCC.


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