The function of Piezo1 in hepatoblastoma metastasis and its potential transduction mechanism

Hepatoblastoma (HB) is the most common primary malignant liver tumor in children. The prognosis of HB metastasis is poor, despite the increasing diversity of treatment. Piezo, a ubiquitously expressed membrane mechano-transduction protein, is involved in the process of tumor cell migration. Under the gene expression profiling interactive analysis (GEPIA) database, Piezo1 was highly expressed in HB and negatively correlated with the overall survival time.

Firstly, the expression of Piezo1 in both paracancerous and HB tissues (n = 7) was detected, and the prognostic value of Piezo1 was assessed in HB (n = 160) patients. Secondly, the inhibition and overexpression of Piezo1were executed in two HB cell lines, HepG2 and Huh 6. Methyl thiazolyl tetrazolium (MTT), wound healing and trans-well assays were performed to identify the effect of Piezo1 on the proliferation and metastasis of HB cells, respectively. In addition, a co-immunoprecipitation assay was performed to determine whether Piezo1 has an interaction with HIF-1α. Finally, the expressions level of Piezo1, HIF-1α, and VEGF by overexpression/inhibition each other were detected by RT-qPCR and western blots to find a possible signaling channel in HB metastasis.

We found that Piezo1 was highly expressed in HB tissues and associated with poor prognosis of patients. Piezo1 was related to cell proliferation in HepG2 and Huh 6 cells. We also found that Piezo1 stimulated HIF-1α expression. Meanwhile, overexpression of Piezo1 promoted the migration and invasion of HB cells, while the promotion was not detected when HIF-1α was suppressed. Additionally, the silencing of HIF-1α inhibited the expression of VEGF, but showed no effect on Piezo1 expression.

In this study, we identified that Piezo1 was involved in HB metastasis, and the Piezo1-HIF-1α-VEGF axis could be a possible signaling pathway in HB metastasis.