RESUMEN
Lung cancer is one of the most common types of cancer and has a high mortality rate, worldwide. The major histopathological subtype is nonsmall cell lung cancer (NSCLC). The aim of the present study was to investigate the role of long noncoding (lnc) RNA PITPNA antisense RNA 1 (PITPNAAS1) in NSCLC and elucidate its potential mechanisms. The expression of PITPNAAS1 was determined in several NSCLC cell lines. Following PITPNAAS1silencing, cell proliferation, invasion and migration were evaluated using Cell Counting Kit8, colony formation, Transwell assay and wound healing assays, respectively. The expression levels of proliferation, migration and epithelialmesenchymal transition (EMT)associated proteins were examined using immunofluorescence assay or western blot analysis. A luciferase reporter assay was conducted to verify the potential interaction between PITPNAAS1 and microRNA(miR)325p. Subsequently, rescue assays were performed to investigate the effects of PITPNAAS1 and miR325p on NSCLC progression. The results demonstrated that PITPNAAS1 was highly expressed in NSCLC tissues and cell lines. It was found that PITPNAAS1 silencing inhibited the proliferation, invasion and migration of NSCLC cells. Furthermore, the protein expression of Ecadherin was upregulated, while the expression levels Ncadherin and vimentin were downregulated. The luciferase reporter assay confirmed that miR325p was a direct target of PITPNAAS1. The rescue experiments suggested that a miR325p inhibitor significantly reversed the inhibitory effects of PITPNAAS1 silencing on proliferation, invasion, migration and EMT in NSCLC cells. Collectively, the present results demonstrated that PITPNAAS1 silencing could suppress the progression of NSCLC by targeting miR325p, suggesting a promising biomarker in NSCLC diagnosis and treatment.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proliferación Celular , Transición Epitelial-Mesenquimal , Silenciador del Gen , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/genética , MicroARNs/genética , Metástasis de la Neoplasia , ARN Largo no Codificante/genética , ARN Neoplásico/genéticaRESUMEN
Plenty of reports have probed the involvement of abnormally expressed lncRNAs in multiple cancers, including lung squamous cell carcinoma (LUSC). Through online database GEPIA, lncRNA PITPNA antisense RNA 1 (PITPNA-AS1) was highly expressed in LUSC samples, and these tendency was further affirmed in LUSC cells. The aim of current study was to investigate the related mechanism of PITPNA-AS1 in LUSC. Functional experiments verified that depletion of PITPNA-AS1 hampered the proliferative and migratory abilities, but accelerated apoptosis of LUSC cells. Additionally, we observed the increased expression of HMGB3 and its positive correlation with PITPNA-AS1 in LUSC samples. Interestingly, PITPNA-AS1 mainly located in the cytosol of LUSC cells, and also affected mRNA stability of HMGB3. Furthermore, the repressed mRNA stability of HMGB3 by PITPNA-AS1 via TAF15 was exposed through mechanism experiments. The mediatory function of PITPNA-AS1 on HMGB3 was validated via rescue assays. All in all, PITPNA-AS1 promoted the proliferation and migration of LUSC cells via stabilizing HMGB3 by TAF15. In conclusion, our study displayed a novel mechanism underlying PITPNA-AS1 in LUSC cells.