Bioinformatics analysis of the association between miR-942-5p–induced downregulation of PIEZO-type mechanosensitive ion channel component 1 and poor prognosis in non–small cell lung cancer mediated by the mitogen-activated protein kinase pathway sign

Abstract Background Non–small cell lung cancer (NSCLC) is a common malignant tumor with an increasing incidence. PIEZO-type mechanosensitive ion channel component 1 (PIEZO1) is a mechanosensitive ion channel whose expression has been implicated in various cancers. However, its expression patterns, prognostic implications, and specific molecular mechanisms of action in NSCLC remain unclear. This study aimed to characterize the expression profile of PIEZO1 in NSCLC in vitro and using bioinformatics analyses. Methods To determine the expression profile of PIEZO1 in normal and cancerous human tissues and the mRNA expression of PIEZO1 in NSCLC, we analyzed data from The Cancer Genome Atlas. Various bioinformatics analyses were performed for correlation analyses, construction of survival curves, and identification of upstream mRNA targets and genes coexpressed with PIEZO1. Furthermore, the coexpressed genes were functionally annotated with Gene Ontology and subjected to pathway enrichment analyses. Additionally, we analyzed and compared PIEZO1 expression in normal and cancerous human tissue samples in vitro. Results NSCLC tissue samples had lower PIEZO1 expression than adjacent tissues. PIEZO1 overexpression inhibited NSCLC progression and cell migration and correlated with improved survival outcomes, as revealed by bioinformatics analyses. Additionally, analysis using the OncomiR database revealed that miR-942-5p upregulation contributed to the downregulation of PIEZO1 in NSCLC. Mechanistic investigations suggested that PIEZO1 modulates NSCLC by regulating the mitogen-activated protein kinase pathway, particularly by targeting FLNA, RRAS, and MAP3K6. Bioinformatics analyses highlighted the potential of PIEZO1 as a therapeutic target and prognostic indicator of NSCLC. Conclusions These novel findings reveal the expression profile of PIEZO1 in NSCLC and highlight the potential of PIEZO1 and miR-942-5p as diagnostic and therapeutic biomarkers of NSCLC and other cancer types.