Progressive liver fibrosis is the primary cause of liver cirrhosis and hepatocellular carcinoma, and leads to considerable morbidity and mortality. Recent studies have demonstrated that microRNAs (miRNAs or miRs) are associated with fibrotic processes in liver disorders, although the exact role of miR-219 remains unclear and the relevant mechanisms remain to be completely understood. To the best of our knowledge, the present study was the first to demonstrate the functional implications of miR-219 expression during liver fibrosis. The present study reported that miR-219 exhibited significantly reduced expression in serum from patients and that its expression was negatively associated with clinical stage. It was also demonstrated that miR-219 attenuated angiotensin II-induced expression of pro-fibrotic markers, including α-smooth muscle actin, atlastin GTPase 1 and collagen. Additionally, a CCl4-induced mouse liver injury model was used to demonstrate that miR-219 strongly suppressed liver fibrosis in vivo . Furthermore, the present study identified tumor growth factor β receptor 2 (TGFBR2) as a direct target gene of miR-219. In conclusion, the results of the present study revealed that miR-219 may regulate pro-fibrotic markers by directly targeting the TGFBR2 gene and the miR-219/TGFBR2 signaling pathway may be a potential therapeutic target for liver fibrosis.

Long noncoding RNA MCF2L-AS1 functions in the development of cancers like lung cancer, ovarian cancer, and colorectal cancer. Notwithstanding, its function in hepatocellular carcinoma (HCC) stays obscure. Our research probes its role in MHCC97H and HCCLM3 cell proliferation, migration, and invasion. qRT-PCR gauged MCF2L-AS1 and miR-33a-5p expressions in HCC tissues. CCK8, colony formation, Transwell, and EdU assays detected HCC cell proliferation, invasion, and migration, respectively. The xenograft tumor model was built to confirm the MCF2L-AS1-mediated role in HCC cell growth. Western blot and immunohistochemistry detected FGF2 expression in HCC tissues. Bioinformatics analysis predicted the targeted relationships between MCF2L-AS1 or FGF2 and miR-33a-5p, which were further examined through dual-luciferase reporter gene and pull-down assays. MCF2L-AS1 was expressed highly in HCC tissues and cells. MCF2L-AS1 upregulation enhanced HCC cells’ proliferation, growth, migration, and invasion and reduced apoptosis. miR-33a-5p was demonstrated as an underlying target of MCF2L-AS1. miR-33a-5p impeded HCC cells’ malignant behaviors. MCF2L-AS1 overexpression reversed miR-33a-5p-mediated effects. MCF2L-AS1 knockdown enhanced miR-33a-5p and negatively regulated FGF2 protein. miR-33a-5p targeted and inhibited FGF2. miR-33a-5p overexpression or FGF2 knockdown inhibited MCF2L-AS1-mediated oncologic effects in MHCC97H. By modulating miR-33a-5p/FGF2, MCF2L-AS1 exerts a tumor-promotive function in HCC. The MCF2L-AS1-miR-33a-5p-FGF2 axis may provide new therapeutic targets for HCC treatment.