Exosomal microRNA-448 suppresses the malignant behaviors of liver cancer cells by targeting RAB7A and inhibiting glycolysis.

Liver cancer is a highly aggressive cancer and the regulatory roles of microRNAs (miRs) in its progression are still being explored. miR-448, which is implicated in several types of cancer, remains to be fully characterized in liver cancer, particularly regarding its presence in exosomes. The aim of the present study was to examine the effects of exosomal miR-448 (EXO-miR-448) on liver cancer cell behavior. The expression levels of miR-448 in human liver cancer cell lines and its localization in exosomes were analyzed using reverse transcription-quantitative PCR, transmission electron microscopy and nanoparticle tracking analysis, with western blotting performed to detect exosomal markers. Functional assays were conducted to assess the effects of EXO-miR-448 on cell proliferation, migration and invasion. The results demonstrated that miR-448 expression was significantly downregulated in human liver cancer cell lines (HepG2, Hep3B and SK-HEP-1) compared with that in normal liver cells. Furthermore, exosomal analysis confirmed that miR-448 was enriched within exosomes rather than being secreted into the supernatant. EXO-miR-448 also inhibited liver cancer cell proliferation, migration and invasion, as demonstrated using Cell Counting Kit-8 and Transwell assays. Bioinformatics and functional assays further identified Ras-related protein Rab-7a (RAB7A) as a direct downstream target of miR-448, with its overexpression rescuing the inhibitory effects of EXO-miR-448 on cell behavior. Furthermore, EXO-miR-448 suppressed glycolysis in liver cancer cells by targeting RAB7A, as indicated by reduced lactate production, glucose uptake, ATP levels and extracellular acidification rate. In conclusion, EXO-miR-448 inhibits liver cancer cell proliferation, migration, invasion and glycolysis by targeting RAB7A. These findings underscore the importance of miR-448 in liver cancer biology and support its further evaluation in future translational studies.