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Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC.
- Source :
-
Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2013 Mar; Vol. 33 (3), pp. 476-86. - Publication Year :
- 2013
-
Abstract
- Background & Aims: Aberration of miR-129-2 has been linked to a variety of human tumours. However, whether miR-129-2 is involved in hepatocarcinogenesis remains unknown. Here, we investigate the involvement of miR-129-2 in HBV infection-related HCC.<br />Methods: A total of 75 paired tumour and their corresponding non-tumour liver tissues from HCC patients with serum HBsAg positive were collected. The methylation of miR-129-2 gene was quantitatively analysed by a DNA methylation-sensitive endonuclease digestion followed by quantitative PCR. The expression of mature miR-129-2 (miR-129-3p) was detected by Taqman RT-PCR. SOX4 expression was detected using quantitative realtime RT-PCR, western blot and immunohistochemical staining. The function of miR-129-2 was investigated using cell proliferation and clonogenicity assays in vitro.<br />Results: Compared with the adjacent non-tumour tissues, tumour tissues exhibited significantly increased miR-129-2 hypermethylation both in frequency (37.33% vs. 8%, P < 0.0001) and in intensity (14.77% vs. 3.08%, P = 0.002). Accordantly, miR-129-3p expression in HCC tissues was significantly lower than that in non-tumour tissues (P = 0.0461), in a manner reversely correlated with the level of miR-129-2 hypermethylation. Notably, SOX4 level in the HCC tissues was significantly higher than that in non-tumour tissues (P = 0.0174) and normal liver tissues (P = 0.0077), correlated reversely with miR-129-3p level (P = 0.0105). Furthermore, overexpression of miR-129-2 in HepG2 reduced cell proliferation and clonogenicity, while co-expression with SOX4 could partially reverse its antitumor effects. In addition, SOX4 in HepG2 cell can enhance β-catenin/TCF activity by increasing β-catenin level.<br />Conclusion: The current data indicated that methylation-mediated repression of miR-129-2 may enhance oncogenic SOX4 expression and involve in HCC tumorigenesis.<br /> (© 2012 John Wiley & Sons A/S.)
- Subjects :
- Blotting, Western
Carcinoma, Hepatocellular etiology
DNA Primers genetics
Hep G2 Cells
Humans
Immunohistochemistry
Liver Neoplasms etiology
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Carcinoma, Hepatocellular metabolism
DNA Methylation
Gene Expression Regulation, Neoplastic physiology
Hepatitis B complications
Liver Neoplasms metabolism
MicroRNAs antagonists & inhibitors
SOXC Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1478-3231
- Volume :
- 33
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Liver international : official journal of the International Association for the Study of the Liver
- Publication Type :
- Academic Journal
- Accession number :
- 23402613
- Full Text :
- https://doi.org/10.1111/liv.12097