A Putative Tumor Suppressing Role of hsa-miR-154 in Breast Cancer that acts by Targeting CLOCK Gene
Abstract BackgroundMicroRNA-154 (hsa-miR-154) is a novel miRNA. Emerging information shows that hsa-miR-154 participates in multiple physiological and pathological processes and is generally identified as a tumor suppressor in multiple types of cancers. Methylation of the hsa-miR-154 gene could also be altered by circadian disruption associated with night shiftwork. ResultsIn this study, we tested whether hsa-miR-154 expression is downregulated in breast cancer and whether hsa-miR-154 targets any circadian genes. Using publicly available datasets and bioinformatics analysis, we first demonstrated that expression levels of hsa-miR-154 were significantly lower in breast tumors compared to normal breast tissues and its expression correlated with clinical outcomes. Downregulation of hsa-miR-154 was also confirmed in breast cancer cell lines and restoration of hsa-miR-154 by transfection significantly inhibited growth of these cells. Further bioinformatics screening indicated that the circadian gene CLOCK is likely a hsa-miR-154 target. ConclusionsThese findings suggest a potential tumor suppressing role of hsa-miR-154 in breast cancer that acts by targeting CLOCK gene. Exploration of hsa-miR-154 for its anti-cancer effect may provide information on its potential for therapeutic application.