MALAT1/ miR-1-3p-mediated BRF2 promotes HCC progression via inhibiting the LKB1/AMPK signaling pathway

Abstract

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and one of the main causes of cancer-related death worldwide. Many studies have shown that abnormal expression of lncRNA plays a crucial role in HCC. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in various tumors. However, the underlying mechanism of MALAT1 in HCC has not been thoroughly elucidated. The expression of MALAT1 were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 by cell CCK-8, colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure PI3K/Akt and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. We found that MALAT1 was upregulated, and MALAT1 knockdown inhibited migration and invasion, and it induced apoptosis in vitro and in vivo. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B‑related factor 2 (BRF2) which was associated with clinical index and poor prognosis. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge hsa-miR-1-3p, which upregulated BRF2. Knockdown of BRF2 inhibited the progression of HCC by the LKB1/AMPK pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown. Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future.