miR-486-3p mediates hepatocellular carcinoma sorafenib resistance by targeting FGFR4 and EGFR

摘要

Cell viability measured by CCK-8 assay at different time points over 72 h showed that when cells were cultured in the same concentration of sorafenib (10 µM for SK-Hep-1 and Huh7, 7 µM for HepG2). The proliferation of resistant cells was greater than that of their parental cells; ( ) miRNA sequencing of Huh7-SR and Huh7-WT showed a total of 26 miRNAs exhibited significantly different expression between the two groups. Five miRNAs, miR-671-3p, miR-378a-5p, miR-328-3p, miR-486-3p, and miR-378a-3p, were significantly reduced in Huh7-SR cells; ( ) qRT-PCR evaluated the expression of the five candidates in all three resistant cell lines. The results confirmed that these five miRNAs were downregulated, with the exception of , which was higher in Huh7-SR cells; ( ) Cell viability measured by CCK-8 assay demonstrated could consistently suppress resistant cell proliferation in all three resistant cells; ( ) HCC prognosis data obtained from Kaplan Meier-plotter showed patients with higher levels in cancer tissue had significantly better overall (HR = 0.38; 95%CI: 0.24 to 0.62  = 3.7e−0.5) and disease-free survival (HR = 0.55; 95%CI: 0.36 to 0.83;  = 0.0037); ( ) Clinical data with 40 pairs of HCC patients showed miR-486-3p levels was significantly lower in tumor tissue than adjacent normal tissue (  = 0.0044).