USP21 And MicroRNA-215 Play Critical Roles In Hepatocellular Carcinoma Progression

Hepatocellular carcinoma is one of the five most common cancers found globally.In China,there are more than 460 thousand new cases and 420 thousand lethal cases,which is a well known cancer and seriously threatens national health.Recently,the treatments and corresponding outcomes are quite limited,which requires the elucidation on the pathogenesis of HCCDeubiquitinases participate in the regulation of various cellular activities,which further affects different types of carcinogenesis.Deubiquitinase USP21 is highly expressed in HCC tissues through analyzing online databases.Experiments support that overexpression of USP21 promotes HCC cell proliferation and transformation,while its knock-down or knock-out inhibits.Furthermore,USP21 is found to interact with MEK2 and stabilizes MEK2 protein level by deubiquitination.As MEK2 is a critical kinase of the ERK pathway,the stabilization of MEK2 protein by USP21 activates the ERK pathway,which affects the hepatocarcinogenesis and development.Abnormal expression of microRNA(miRNA)substantially affects various carcinoma genesis.Through analysis on miRNA expression map in two control cell lines and two HCC cell lines,we find that miR-215 in HCC cell lines exhibits a high expression level verified by real-time PCR,in comparison to control cell lines.Overexpression of miR-215 in HCC promotes the cancer cell migration and transformation,while the inhibition of miR-215 shows contrary effects.Dicerl is the essential enzyme for the modification and maturation of miRNA.What's more,miR-215 is found to directly target the 3'-UTR of Dicer1 and inhibit its protein expression.With the inhibition of Dicerl,expressions of amounts of tumor suppressor miRNAs are subsequently inhibited,which promotes cell migration and transformation.Real-time PCR verifies that Dicer1 expresses significantly lower in the HCC tissues compared with adjacent tissues.The study here first finds the high expression of miR-215 in HCC cells,and also reveals that the direct regulation of miR-215 on Dicer1 is associated with HCC malignant development.In summary,USP21 and miR-215 participate in the regulation of hepatocarcinogenesis and development,which are beneficial for clarification of the molecular mechanisms of hepatocarcinogenesis,as well as developing effective clinical treatments.