Abstract:
Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, exerts a significant burden on Southeast Asian countries and stands as the third leading cause of cancer-related mortality worldwide. Despite this alarming impact, effective treatments for HCC are lacking, resulting in low survival rates and high recurrence rates. Therefore, a comprehensive understanding of the disease's underlying mechanisms is crucial for the development of novel and potent therapies. Recently, it has been recognized that microRNAs (miRNAs) play a vital role in tumorigenesis, including HCC. Our bioinformatic analysis has highlighted hsa-miR-885-5p as a potential candidate miRNA due to its downregulation in HCC tissue compared to normal tissue, particularly in higher-grade tumors. This intriguing finding prompted our study to investigate the function of hsa-miR-885-5p in HCC. In our research, we employed functional assays to demonstrate that hsa-miR-885-5p effectively suppresses cell proliferation and hinders the critical G1/S transition, a crucial step initiating cell proliferation. Through meticulous miRNA target prediction analysis, we identified CDK6, a gene associated with the G1/S transition, as a potential target of hsa-miR-885-5p. Further experimental validation confirmed that hsa-miR-885-5p directly targets CDK6, leading to reduced expression levels and perturbations in protein levels. Moreover, we conducted RNA-seq analysis, which not only supported the involvement of hsa-miR-885-5p in cell cycle processes but also indicated its potential as a negative regulator of the G1/S transition. These findings collectively highlight the interesting role of hsa-miR-885-5p in HCC, potentially through its interaction with CDK6. Consequently, further investigations into the precise functions and therapeutic potential of hsa-miR-885-5p are warranted to unlock its full therapeutic value in HCC.