Piezo1 Promoted Hepatocellular Carcinoma Progression and EMT Through Activating TGF-β Signaling by Recruiting Rab5c

Abstract

Background Piezo1 plays critical roles in vascular development during early embryogenesis. However, the function of Piezo1 in hepatocellular carcinoma (HCC) remain elusive. This study aimed to explore the function and mechanisms of Piezo1 in HCC. Methods qRT-PCR, western blot and immunohistochemistry analyses were used to determine Piezo1 expression in HCC samples and cell lines. The clinical significance of Piezo1 was assessed in two independent study cohorts containing 280 patients with HCC. Gene set enrichment analysis (GSEA) was performed to explore the signaling pathway of Piezo1. A series of in vitro and in vivo experiments were used to determine the role and molecular mechanism of Piezo1 in HCC progression. Results Piezo1 expression was significantly upregulated in HCC tissues and cell lines. High Piezo1 expression was closely correlated with aggressive clinicopathological features, poor clinical outcomes of HCC patients. Moreover, knockdown of Piezo1 in HCCLM3 and Hep3B cells significantly inhibited proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of HCC cells in vitro, and tumor growth, EMT and metastasis in vivo. Further mechanism study indicated that these phenotypic and function changes were mediated by TGF-β signaling pathway. Finally, we proved that Piezo1 exerted its tumor promotion effect by recruiting Rab5c to activating TGF-β signaling pathway. Conclusions We proved Piezo1 promotes progression of hepatocellular carcinoma via TGF-β signaling, which may serve as a novel prognostic predictor and the potential therapeutic target for HCC patients.

Long Non-Coding RNA BCAR4 Promotes Oxaliplatin Resistance in Colorectal Cancer by Modulating miR-484-3p/RAB5C Expression

“…Previous studies have shown that RAB5C is involved in tumorigenesis by promoting tumor cell migration [48]. We found that the expression of RAB5C was increased in CRC tumor tissues, which is consistent with previous studies which showed the increased expression of RAB5C in tumor tissues [48,49]. Interestingly, the expression level of RAB5C was positively correlated with BCAR4.…”