Bioinformatics in vivo and in vitro assays identified miR-486-5p as a tumor suppressor miRNA in hepatocellular carcinoma

Background: This study aimed to explore key microRNAs (miRNAs) and their effects on hepatocellular carcinoma (HCC) progression.

Methods: Key deregulated miRNAs in HCC were screened from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The anti-cancer effects of miR-486-5p were validated using a cell counting kit-8 assay, flow cytometry, scratch assay, transwell assay, and an orthotopic transplantation tumor model. Furthermore, the expression, clinical significance, and function of miR-486-5p and its targets were predicted using bioinformatics. Additionally, a luciferase reporter assay was performed to validate the miR-486-5p target.

Results: By integrating multiple datasets from TCGA and GEO databases, we identified miR-486-5p as the only lowly expressed miRNA in HCC, whose expression was also associated with clinical features. Additionally, miR-486-5p exhibited anti-cancer properties both in vitro and in vivo. Ser/Arg-rich splicing factor 3 (SRSF3) was the predicted target of miR-486-5p, and this finding was further supported by correlation analysis, quantitative polymerase chain reaction, and luciferase reporter assays. Furthermore, SRSF3 expression was upregulated, and high SRSF3 expression was correlated with poor survival in patients with HCC. According to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis, SRSF3 promotes cancer-related pathways.

Conclusion: miR-486-5p suppresses cancer progression in HCC by interacting with SRSF3. Therefore, miR-486-5p and SRSF3 may serve as promising therapeutic targets for HCC treatment.