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 in vivo. The mRNA expression of PIEZO1 and 2 was clearly decreased in NSCLC tumor tissue compared with that in matched adjacent non-tumor tissue. In human NSCLC tissues, PIEZO1 gene expression exhibits a highly deep deletion rate, and PIEZO2 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 PIEZO1 or PIEZO2 in NSCLC cells significantly promoted cell migration in vitro and tumor growth in vivo. 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.
Highlights
Lung cancer (LC) is one of the major causes of deaths worldwide, killing 8.2 million people annually [1]
PIEZO2 is important in touch sensation and the airway stretch sensation mediated by sensory neurones [19–21]
The analysis indicated that mRNA expression of PIEZO1 and 2 in Non-small cell LC (NSCLC) tissues was significantly lower than that in non-tumor tissues (P
Summary
Lung cancer (LC) is one of the major causes of deaths worldwide, killing 8.2 million people annually [1]. Like other cancers, it is characterized by the rapid division and uncontrolled growth of cells, in this instance, in lung tissue. Non-small cell LC (NSCLC) represents 85–90% of all LC, and mainly includes lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) [1]. Heavy metals, genotoxic agents, cigarette smoke, and other non-genetic factors are associated with NSCLC [2,3]. A covalent carcinogen—DNA adduct may result in LC by causing misincorporation leading to genetic mutations [4]. Research focussing on genetic reasons for NSCLC has demonstrated that epidermal growth factor receptor (EGFR) is the most commonly mutated protein that results in LC. 90% of EGFR mutations in LC are a result of deletion in exon 19 affecting either the conserved sequence
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