LncRNA PITPNA-AS1/miR-223-3p/PTN axis regulates malignant progression and stemness in lung squamous cell carcinoma.

Abstract

BackgroundLong noncoding RNAs (lncRNAs) are a kind of molecule that cannot code proteins, and their expression is dysregulated in diversified cancers. LncRNA PITPNA‐AS1 has been shown to act as a tumor promoter in a variety of malignancies, but its function and regulatory mechanisms in lung squamous cell carcinoma (LUSC) are yet unknown.MethodsThe mRNA and protein expression of genes were examined by RT‐qPCR, western blot, and IHC assay. The cell proliferation, migration, invasion, and stemness were detected through CCK‐8, colony formation, Transwell and spheroid formation assays. The CD44+ and CD166+‐positive cells were detected through flow cytometry. The binding ability among genes through luciferase reporter and RNA pull‐down assays. The tumor growth was detected through in vivo nude mice assay.ResultsThe lncRNA PITPNA‐AS1 had increased expression in LUSC and was linked to a poor prognosis. In LUSC, PITPNA‐AS1 also enhanced cell proliferation, migration, invasion, and stemness. This mechanistic investigation showed that PITPNA‐AS1 absorbed miR‐223‐3p and that miR‐223‐3p targeted PTN. MiR‐223‐3p inhibition or PTN overexpression might reverse the inhibitory effects of PITPNA‐AS1 suppression on LUSC progression, as demonstrated by rescue experiments. In addition, the PITPNA‐AS1/miR‐223‐3p/PTN axis accelerated tumor development in vivo.ConclusionsIt is the first time we investigated the potential role and ceRNA regulatory mechanism of PITPNA‐AS1 in LUSC. The data disclosed that PITPNA‐AS1 upregulated PTN through sponging miR‐223‐3p to enhance the onset and progression of LUSC. These findings suggested the ceRNA axis may serve as a promising therapeutic biomarker for LUSC patients.