Five miRNAs-mediated PIEZO2 downregulation, accompanied with activation of Hedgehog signaling pathway, predicts poor prognosis of breast cancer
Five miRNAs-mediated PIEZO2 downregulation, accompanied with activation of Hedgehog signaling pathway, predicts poor prognosis of breast cancer
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五种 miRNA 介导的 PIEZO2 下调，伴随着 Hedgehog 信号通路的激活，预测乳腺癌的不良预后
DOI：
10.18632/aging.101934
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发表时间：
2019-05-15
期刊：
影响因子：
5.2
通讯作者：
Fan, Weimin
中科院分区：
文献类型：
--
作者：
Lou, Weiyang;Liu, Jingxing;Fan, Weimin
压电型机械敏感离子通道元件2(Piezo2)在癌症中的作用仍不清楚。在此，我们探讨了Piezo2在肿瘤中的表达、预后及其可能机制。Piezo2在乳腺中的表达水平高于其他人体组织，因此被选为候选研究对象。接下来，我们发现Piezo2在乳腺癌中的表达低于正常对照，并且发现Piezo2的表达与雌激素受体(ER)和孕激素受体(PR)状态呈正相关，而与人表皮生长因子受体2(HER2)状态、诺丁汉预后指数(NPI)评分、Scarff-Bloom-Richardson(SBR)分级、基底样和三阴性状态呈负相关。随后的分析表明，Piezo2的高表达在乳腺癌中具有良好的预后。预测有182个miRNAs靶向Piezo2。在这些miRNAs中，有5个miRNAs(miR-130b-3p、miR-196a-5p、miR-301a-3p、miR-421和miR-454-3p)具有最大的靶向Piezo2的潜力。共鉴定了109个Piezo2共表达基因。途径富集法分析表明，这些基因在Hedgehog信号通路中有丰富的表达，包括细胞黏附分子相关/癌基因下调(CDON)。CDON在乳腺癌中表达降低，提示预后不良。综上所述，这些发现表明Piezo2的低表达可能被用作乳腺癌预后的生物标志物。
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.