Unknown

Dataset Information

0

MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib.


ABSTRACT: MicroRNAs are negative regulators of protein coding genes. The liver-specific microRNA-122 (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 an epithelial phenotype that correlated with reduced Vimentin expression. ADAM10 (a distintegrin and metalloprotease family 10), serum response factor (SRF), and insulin-like growth factor 1 receptor (Igf1R) 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 up-regulation 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, ADAM10, SRF, and Igf1R were up-regulated in primary human HCCs compared with 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.

SUBMITTER: Bai S 

PROVIDER: S-EPMC2797273 | BioStudies | 2009-01-01

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6406326 | BioStudies
1000-01-01 | S-EPMC4426788 | BioStudies
2019-01-01 | S-EPMC6791887 | BioStudies
2014-01-01 | S-EPMC4277479 | BioStudies
2012-01-01 | S-EPMC3408748 | BioStudies
2020-01-01 | S-EPMC7106760 | BioStudies
1000-01-01 | S-EPMC3132845 | BioStudies
2020-01-01 | S-EPMC7044666 | BioStudies
2014-01-01 | S-EPMC4462359 | BioStudies
1000-01-01 | S-EPMC4494934 | BioStudies