hsa-miR-122

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:

ADAM-10, SRF, Igf1R

Validated targets of miRNA from TarBase:

CAT-1 : More...

Description:

The liver specific miR-122 is frequently suppressed in primary hepatocellular carcinomas (HCCs). In situ hybridization demonstrated that miR-122 is abundantly expressed in hepatocytes, but barely detectable in primary human HCCs. Ectopic expression of miR-122 in nonexpressing HepG2, Hep3B and SK-Hep-1 cells reversed their tumorigenic properties such as growth, replication potential, clonogenic survival, anchorage independent growth, migration, invasion and tumor formation in nude mice. Further, miR-122 expressing HCC cells retained epithelial phenotype that correlated with reduced Vimentin expression. ADAM-10 (a distintegrin and metalloprotease family-10), SRF (serum response factor), and Igf1R (insulin like growth factor 1 receptor) that promote tumorigenesis were validated as targets of miR- 122 and were repressed by the microRNA. Conversely, depletion of the endogenous miR-122 in Huh-7 cells facilitated their tumorigenic properties with concomitant upregulation of these targets. Expression of SRF or Igf1R partially reversed tumor suppressor function of miR-122. Further, miR-122 impeded angiogenic properties of endothelial cells in vitro. Notably, ADAM-10, SRF and Igf1R were upregulated in primary human HCCs compared to the matching liver tissue. Co-labeling studies demonstrated exclusive localization of miR-122 in the benign livers whereas SRF predominantly expressed in HCC. More importantly, growth and clonogenic survival of miR-122 expressing HCC cells were significantly reduced upon treatment with sorafenib, a multi-kinase inhibitor clinically effective against HCC. Collectively, these results suggest that the loss of multifunctional miR-122 contributes to the malignant phenotype of HCC cells and miR-122 mimetic alone or in combination with anticancer drugs can be a promising therapeutic regimen against liver cancer.

Reference:

MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to Sorafenib | PMID:19726678
Bai S, Nasser MW, Wang B, Hsu SH, Datta J, Kutay H, Yadav A, Nuovo G, Kumar P, Ghoshal K.
J Biol Chem. 2009 Sep 2. [Epub ahead of print]