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

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.

• Authors: Iryna Kindrat, Volodymyr Tryndyak, Aline de Conti, Svitlana Shpyleva, Thilak K Mudalige, Tetyana Kobets, Anna M Erstenyuk, Frederick A Beland, Igor P Pogribny
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 2 Pg. 1276-87 (Jan 12 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26657500 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD
• CD71 antigen
• Carcinogens
• MIRN152 microRNA, human
• MicroRNAs
• Receptors, Transferrin
• Tfrc protein, rat
• 2-Acetylaminofluorene

Topics

• 2-Acetylaminofluorene (toxicity)
• Animals
• Antigens, CD (genetics, metabolism)
• Blotting, Western
• Carcinogenesis (drug effects, genetics)
• Carcinogens (toxicity)
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Hep G2 Cells
• Humans
• Liver Neoplasms (genetics, metabolism, pathology)
• Liver Neoplasms, Experimental (chemically induced, genetics, metabolism)
• Male
• MicroRNAs (genetics)
• Rats, Sprague-Dawley
• Receptors, Transferrin (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction