Arash Letafati - Department of Virology, School of Public Health, Tehran University ofMedical Sciences, Tehran, Iran

MicroRNAs (miRNAs), which are inhibitors of gene expression, participatein diverse biological functions and in carcinogenesis. In this study, we show that liverspecificmicroRNA-۱۲۲ (miR-۱۲۲) is significantly down-regulated in liver cancers withintrahepatic metastasis and negatively regulates tumorigenesis. Restoration of miR-۱۲۲in metastatic Mahlavu and SK-HEP-۱ cells significantly reduced in vitro migration,invasion, and anchorage-independent growth as well as in vivo tumorigenesis,angiogenesis, and intrahepatic metastasis in an orthotopic liver cancer model. Becausean inverse expression pattern is often present between an miRNA and its target genes,we used a computational approach and identified multiple miR-۱۲۲ candidate targetgenes from two independent expression microarray datasets. Thirty-two target geneswere empirically verified, and this group of genes was enriched with genes regulatingcell movement, cell morphology, cell-cell signaling, and transcription.Material and Methods: Our aim of this study was to investigate the GBS and itsrelationship with viruses. The search strategy performed in PubMed, NCBI, GoogleScholar, EMBASE and Medline on Cancer and oxidative stress and Gene manipulation upto ۱۰ June ۲۰۲۲ by searching the following keywordsResults: We further showed that one of the miR-۱۲۲ targets, ADAM۱۷ (a dis-integrinand metalloprotease ۱۷) is involved in metastasis. Silencing of ADAM۱۷ resulted in adramatic reduction of in vitro migration, invasion, in vivo tumorigenesis, angiogenesis,and local invasion in the livers of nude mice, which is similar to that which occurs withthe restoration of miR-۱۲۲.Conclusion: Our study suggests that miR-۱۲۲, a tumor suppressor microRNA affectinghepatocellular carcinoma intrahepatic metastasis by angiogenesis suppression, exertssome of its action via regulation of ADAM۱۷. Restoration of miR-۱۲۲ has a far-reachingeffect on the cell. Using the concomitant down-regulation of its targets, includingADAM۱۷, a rational therapeutic strategy based on miR-۱۲۲ may prove to be beneficialfor patients with hepatocellular carcinoma.

MicroRNA, Hepatocellular Carcinoma, Cancer, MiR-۱۲۲