4.6 Article

MCF2L-AS1 promotes the biological behaviors of hepatocellular carcinoma cells by regulating the miR-33a-5p/FGF2 axis

Journal

AGING-US
Volume 15, Issue 13, Pages 6100-6116

Publisher

IMPACT JOURNALS LLC

Keywords

hepatocellular carcinoma; MCF2L-AS1; miR-33a-5p; FGF2

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Long noncoding RNA MCF2L-AS1 plays a role in the development of various cancers, but its function in hepatocellular carcinoma (HCC) was unclear. This study investigated its role in HCC cell proliferation, migration, and invasion. MCF2L-AS1 was highly expressed in HCC tissues and cells, and its upregulation enhanced HCC cell behaviors while reducing apoptosis. miR-33a-5p was identified as a target of MCF2L-AS1 and inhibited HCC cell behaviors. The MCF2L-AS1-miR-33a-5p-FGF2 axis may be a potential therapeutic target for HCC treatment.
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.

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