EFFECT OF MIRNA-133B ON HEPATOCELLULAR CARCINOMA PROLIFERATION AND MIGRATION VIA REGULATING THE SF3B4 SIGNALING PATHWAY

Objective: To explore the effect of microRNA-133b (iniRNA-133b) on hepatocellular carcinoma proliferation and migration via regulating the splicing factor 3b subunit 4 (SF3B4) signaling pathway. Methods: Fifty-six cases of liver cancer tissues and 24 cases of normal adjacent tissues archived in the Department of Pathology of our hospital from January 2017 to January 2018 were selected, and the mRNA expression of SF3B4 in liver cancer tissues and normal adjacent tissues was detected by RT-PCR. Human liver cancer cell lines Huh7 and SMMC-772 were collected. All liver cancer cell lines of Huh7 and some liver cancer cell lines of SMMC-772 were taken. The samples were randomly divided into a pcDNA3.1 group (empty vector; negative control), a pcDNA3.1-SF3B4 group (overexpressed SF3B4), and an RNAi group (knockout SF3B4). The proliferation ability of Huh7 and SMMC-7721 cells in the pcDNA3.1 group and the pcDNA3.1-SF3B4 group were compared. At the same time, the migration ability of the pcDNA3.1 group, the pcDNA3.1-SF3B4 group, the RNAi group Huh7, and the SMMC-7721 cells was compared at 0 h, 36 h, and 48 h. The remaining liver cancer of cell line SMMC-772 was taken as the miRNA-133b group (over-expressing SF3B4, miRNA-133b). The protein expression levels of SMMC-7721 cells in the miRNA-133b group and the pcDNA3.1-SF3B4 group, which are proliferation-related indicators of the SF3B4 signaling pathway [Kruppel-like factor 4 (KLF4), Cyclin-dependent kinase inhibitor 1 B (KlPl), SF3B4, Snail family transcription inhibitor 2 (SNA12)], were compared. At the same time, the migration ability of cancer cells in the miRNA-133b group and the pcDNA3.1-SF3B4 group was compared at 0 h, 36 h and 48 h. Results: SF3B4 mRNA in liver cancer tissues was significantly higher than in normal adjacent tissues, and miRNA-133b mRNA was significantly lower than in normal adjacent tissues (P<0.01).The proliferation ability of pcDNA3.1-SF3B4 liver cancer cells Huh7 and SMMC-7721 was significantly higher than the pcDNA3.1 group (P<0.05 I. At 36 h and 48 h, the migration ability of liver cancer cells Huh7 and SMMC-7721 in the pcDNA3.1-SF3B4 group was significantly higher than in the pcDNA3.1 group (P<0.001). The proliferation ability of Huh7 and SMMC-7721 cells in the RNAi group was significantly lower than in the pcDNA3.1 group (P<0.05 I. At 36 h and 48 h, the migration ability of liver cancer cells Huh7 and SMMC-7721 in the RNAi group was significantly lower than in the pcDNA3.1 group (P<0.05). The proliferation rate of SMMC-7721 in the miRNA-1336 group was significantly lower than in the pcDNA3.1-SF3B4 group (P<0.05). At 36 h and 48 h, the migration ability of liver cancer cell SMMC-7721 in the miRNA-133b group was significantly lower than in the pcDNA3.1-SF3B4 group (P<0.05). The expression levels of KLF4 and KIPI protein in miRNA-133b liver cancer cells SMMC-7721 were significantly higher than those in the pcDNA3.1-SF3B4 group, and the expression levels of SF3B4 and SNAl2 proteins were significantly lower than those in the pcDNA3.1-SF3B4 group (P<0.05). Conclusions: miRNA-133b is expressed at a low level in liver cancer tissues, and SF3B4 is highly expressed in liver cancer tissues. Up-regulating the expression of miRNA-133b could inhibit SF3B4-related signaling pathways, thereby hindering liver cancer cell proliferation and migration, and be used as a potential new target for liver cancer treatment.