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Methylation-mediated repression of micro RNA 129-2 enhances oncogenic SOX4 expression in HCC.
- Source :
- Liver International; Mar2013, Vol. 33 Issue 3, p476-486, 11p, 1 Chart, 6 Graphs
- 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. Methods A total of 75 paired tumour and their corresponding non-tumour liver tissues from HCC patients with serum HBs Ag 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. 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. Conclusion The current data indicated that methylation-mediated repression of miR-129-2 may enhance oncogenic SOX4 expression and involve in HCC tumorigenesis. [ABSTRACT FROM AUTHOR]
- Subjects :
- METHYLATION
RNA
GENE expression
LIVER cancer
CELL proliferation
DNA methylation
Subjects
Details
- Language :
- English
- ISSN :
- 14783223
- Volume :
- 33
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Liver International
- Publication Type :
- Academic Journal
- Accession number :
- 85431428
- Full Text :
- https://doi.org/10.1111/liv.12097