hsa-miR-1

hepatocellular carcinoma (HCC)

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

down-regulated

Validated targets of miRNA from the reference:

FoxP1, MET, HDAC4

Validated targets of miRNA from TarBase:

GJA1,Hand2,HDAC4,TMSB4X : More...

Description:

The CGI spanning exon 1 and intron 1 of miR-1-1 was methylated in HCC cell lines and in primary human HCCs but not in matching liver tissues. The miR-1-1 gene was hypomethylated and activated in DNMT1-/- HCT 116 cells but not in DNMT3B null cells, indicating a key role for DNMT1 in its methylation. miR-1 expression was also markedly reduced in primary human hepatocellular carcinomas compared with matching normal liver tissues. Ectopic expression of miR-1 in HCC cells inhibited cell growth and reduced replication potential and clonogenic survival. The expression of FoxP1 and MET harboring three and two miR-1 cognate sites, respectively, in their respective 3'-untranslated regions, was markedly reduced by ectopic miR-1. Up-regulation of several miR-1 targets including FoxP1, MET, and HDAC4 in primary human HCCs and down-regulation of their expression in 5-AzaC-treated HCC cells suggest their role in hepatocarcinogenesis. The inhibition of cell cycle progression and induction of apoptosis after re-expression of miR-1 are some of the mechanisms by which DNA hypomethylating agents suppress hepatocarcinoma cell growth.

Reference:

Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. | PMID:18593903
Datta J, Kutay H, Nasser MW, Nuovo GJ, Wang B, Majumder S, Liu CG, Volinia S, Croce CM, Schmittgen TD, Ghoshal K, Jacob ST.
Cancer Res. 2008 Jul 1;68(13):5049-58.