Five miRNAs-mediated PIEZO2 downregulation, accompanied with activation of Hedgehog signaling pathway, predicts poor prognosis of breast cancer.

Roles of Piezo-type mechanosensitive ion channel component 2 (PIEZO2) in cancer remain largely unknown. Herein, we explored PIEZO2 expression, prognosis and underlying mechanisms in cancer. Breast was selected as the candidate as its relatively higher expression level of PIEZO2 than other human tissues. Next, we identified a decreased expression of PIEZO2 in breast cancer compared with normal controls, and found that PIEZO2 expression positively correlated with estrogen receptor (ER) and progesterone receptor (PR) status but negatively correlated with human epidermal growth factor receptor 2 (HER2) status, Nottingham Prognostic Index (NPI) score, Scarff-Bloom-Richardson (SBR) grade, basal-like and triple-negative status. Subsequent analysis revealed that high expression of PIEZO2 had a favorable prognosis in breast cancer. 182 miRNAs were predicted to target PIEZO2. Among these miRNAs, five miRNAs (miR-130b-3p, miR-196a-5p, miR-301a-3p, miR-421 and miR-454-3p) possess the greatest potential in targeting PIEZO2. 109 co-expressed genes of PIEZO2 were identified. Pathway enrichment analysis showed that these genes were enriched in Hedgehog signaling pathway, including Cell adhesion molecule-related/downregulated by oncogenes (CDON). CDON expression was decreased in breast cancer and downregulation of CDON indicated a poor prognosis. Altogether, these findings suggest that decreased expression of PIEZO2 may be utilized as a prognostic biomarker of breast cancer.