Cancer‐testis gene PIWIL1 promotes cell proliferation, migration, and invasion in lung adenocarcinoma

Abstract Piwi‐like RNA ‐mediated gene silencing 1 ( PIWIL 1 ) has been identified as a novel extremely highly expressed cancer‐testis ( CT ) gene in lung adenocarcinoma. However, the exact function and mechanism of PIWIL 1 in lung adenocarcinoma remains unclear. Herein, we sought to investigate the role of PIWIL 1 in the occurrence and development of lung adenocarcinoma. We examined the expression pattern of PIWIL 1 in The Cancer Genome Atlas ( TCGA ) lung adenocarcinoma samples, and validated it by Real‐Time PCR ( RT ‐ PCR ) in additional 21 paired lung adenocarcinoma tissues and 16 normal tissues. Subsequently, we explored the biological function of PIWIL 1 in A549 and H1299 cell lines by gain and loss‐of‐function analyses. Using TCGA lung adenocarcinoma data, we further performed coexpression and Gene Ontology ( GO ) analyses, and analyzed the association of DNA methylation levels in PIWIL 1 promoter region with its expression. Finally, we evaluated its expression in different mutation status of significantly mutated genes ( SMG s) in TCGA lung adenocarcinoma data. We observed that PIWIL 1 was expressed in testis and lung adenocarcinoma but not in other normal tissues, and its high expression was associated with shortened survival of lung cancer patients. Overexpression of PIWIL 1 could facilitate the proliferation, invasion and migration of lung adenocarcinoma cells and vice versa. GO analysis revealed that PIWIL 1 upregulated genes were enriched in embryonic development, cell proliferation and regulation of transcription. Moreover, promoter DNA hypomethylation of PIWIL 1 could contribute to its aberrant expression in tumors. Interestingly, PIWIL 1 expression was significantly higher in patients without hepatocyte growth factor ( HGF ) or serine/threonine kinase 11 ( STK 11 ) mutation ( P = 0.006 and 0.005, respectively). PIWIL 1 is an epidriver gene in lung adenocarcinoma, indicating a potential target for further therapy.