Effect And Mechanism Of MiR-183-5p On Sorafenib Resistance In Hepatocellular Carcinoma

Objective: To investigate the effect of miR-183-5p on sorafenib resistance in hepatocellular carcinoma(HCC),and whether miR-183-5p regulates HCC sorafenib resistance through the SOCS6/JAK2/STAT3 signaling pathway,providing new ideas,directions and theoretical basis for the clinical diagnosis and treatment of hepatocellular carcinoma.Methods: Conventional methods to culture human normal hepatocyte lines LO2 and hepatoma cell lines Hep G2,Huh7 and MHCC97 H,and miR-183-5p inhibition and overexpression and SOCS6 overexpression of hepatoma cell lines were constructed.The changes of m RNA expression of miR-183-5p and SOCS6 in each group were detected by real-time PCR experiments,the 50% inhibitive concentration(IC50)of each group of cells was detected by CCK-8 experiments,and the apoptosis rate of each group after treatment with sorafenib was detected by flow cytometry.Western blotting detected the protein expression changes of SOCS6,JAK2,p-JAK2,STAT3 and p-STAT3 in each group of cells.Result: Bioinformation analysis showed that miR-183-5p was highly expressed in liver cancer tissues.The results of real-time PCR showed that miR-183-5p was highly expressed in human HCC cell lines,and the expression levels of miR-183-5p in HCC cell lines MHCC97 H,Hep G2 and Huh7 decreased from low to high.SOCS6 m RNA levels were elevated in the miR-183-5p inhibition group compared to the control group.The results of CCK-8 showed that the IC50 values of MHCC97 H,Hep G2 and Huh7 sorafenib of HCC cell lines were from high to low.The IC50 value of sorafenib in the miR-183-5p inhibition group was lower than that in the control group,the IC50 value of sorafenib in the miR-183-5p overexpression group was higher than that in the control group,and the IC50 value in the SOCS6 overexpression group was lower than that in the control group.The results of flow cytometry showed that the apoptosis rate of cells treated with sorafenib in the miR-183-5p inhibited group was higher than that in the control group,the apoptosis rate after sorafenib treatment in the miR-183-5p overexpression group was lower than that in the control group,and the apoptosis rate after sorafenib treatment in the SOCS6 high expression group was higher than that in the control group.Compared with the control group,the expression level of SOCS6 increased,the expression level of p-JAK2 and p-STAT3 decreased,and the protein levels of JAK2 and STAT3 remained unchanged.The SOCS6 overexpression group was consistent with the miR-183-5p inhibitory group.Conclusion: miR-183-5p may be one of the key factors in promoting resistance to sorafenib in hepatocellular carcinoma,and its mechanism may be to promote sorafenib resistance in hepatocellular carcinoma by inhibiting the SOCS6/JAK2/STAT3 signaling pathway.