MiR-135b promotes HCC tumorigenesis through a positive-feedback loop

Hippo pathway plays critical roles in cell proliferation and apoptosis and its dysregulation leads to various types of cancers, including hepatocellular carcinoma (HCC). However, the mechanism maintaining Hippo pathway homeostasis still remains unclear. In this study, we discovered that the expression of miR-135b is apparently upregulated in HCC tissues and HCC cell lines. The level of miR-135b was positively correlated with HCC stages and negatively correlated with the survival of HCC patients, suggesting an oncogenic role of miR-135b in HCC progression. Similarly, miR-135b mimic promoted HCC cell proliferation and migration, whereas its inhibitor played an opposite role. Mechanistically, we identified a seed sequence of miR-135b in the MST1 3'-UTR region. MiR-135b inhibited the Hippo pathway by silencing MST1 expression. Additionally, we revealed that miR-135b was a transcriptional target of the Hippo pathway. Based on these data, we propose that a positive-feedback axis of MST1-YAP-miR-135b exists for HCC aggravation. Our study not only deepens the insight into the Hippo pathway homeostasis, but also suggests miR-135b as a potential prognosis biomarker and therapeutic target for HCC.