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拉伸激活通道 PIEZOs 的缺失会加速非小细胞肺癌的进展和细胞迁移。

Loss of stretch-activated channels, PIEZOs, accelerates non-small cell lung cancer progression and cell migration.

机构信息

Department of Radiology, Jilin Province Cancer Hospital, Changchun, Jilin, China.

Department of Interventional Radiology, Jilin Province Cancer Hospital, Changchun, Jilin, China.

出版信息

Biosci Rep. 2019 Mar 22;39(3). doi: 10.1042/BSR20181679. Print 2019 Mar 29.

Abstract

PIEZO channels are stretch-activated channels involved in wound sealing and cell proliferation in many cell types. A recent study focussing on lung cancer (LC), using next-generation sequencing analysis, has indicated that PIEZO functions were implicated in LC development. However, the expression and role of PIEZO channels in non-small cell LC (NSCLC) progression require elucidation. In the current study, we investigated the gene expression and alteration frequency in human NSCLC tissue, accessed the prognostic roles of PIEZO channels in NSCLC patients, and further studied the effect of PIEZOs in NSCLC cell proliferation and tumor growth The mRNA expression of and was clearly decreased in NSCLC tumor tissue compared with that in matched adjacent non-tumor tissue. In human NSCLC tissues, gene expression exhibits a highly deep deletion rate, and mainly exhibits mutation in gene expression. High mRNA expression of PIEZO channels was found to correlate with better overall survival (OS) for NSCLC patients, especially for patients with lung adenocarcinoma (LUAD), but not for patients with lung squamous cell carcinoma (LUSC). The prognostic role of PIEZO channels was more sensitive in female patients than male patients, and more sensitive in patients at earlier stages than patients at latter stages. Knockdown of or in NSCLC cells significantly promoted cell migration and tumor growth These results indicate the critical prognostic values of the PIEZO channels in NSCLC. This information will be beneficial to understand the pathological mechanism of NSCLC and to generate effective therapeutic approaches for NSCLC patients.

摘要

PIEZO 通道是一种拉伸激活的通道,参与多种细胞类型的伤口密封和细胞增殖。最近一项针对肺癌 (LC) 的研究,使用下一代测序分析表明,PIEZO 功能与 LC 发展有关。然而,PIEZO 通道在非小细胞肺癌 (NSCLC) 进展中的表达和作用需要阐明。在本研究中,我们研究了人类 NSCLC 组织中的基因表达和改变频率,评估了 PIEZO 通道在 NSCLC 患者中的预后作用,并进一步研究了 PIEZOs 在 NSCLC 细胞增殖和肿瘤生长中的作用。与匹配的相邻非肿瘤组织相比,NSCLC 肿瘤组织中 的 mRNA 表达明显降低。在人类 NSCLC 组织中, 基因表达表现出高深度缺失率,而 主要表现为基因表达突变。高 PIEZO 通道 mRNA 表达与 NSCLC 患者的总生存期 (OS) 更好相关,特别是肺腺癌 (LUAD) 患者,但与肺鳞癌 (LUSC) 患者无关。PIEZO 通道的预后作用在女性患者中比男性患者更敏感,在早期患者中比晚期患者更敏感。在 NSCLC 细胞中敲低 或 显著促进细胞迁移 和肿瘤生长。这些结果表明 PIEZO 通道在 NSCLC 中具有重要的预后价值。这些信息将有助于理解 NSCLC 的病理机制,并为 NSCLC 患者生成有效的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e4/6430724/7fc001837ca1/bsr-39-bsr20181679-g1.jpg

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