Abstract
OSER1 antisense RNA 1 (OSER1-AS1), a long noncoding RNA, has been well studied in the context of hepatocellular carcinoma. However, its expression status, specific functions, and tumorigenic mechanism in non-small cell lung cancer (NSCLC) remain uninvestigated. Hence, this study aimed to assess OSER1-AS1 expression, test the malignancy-related biological functions of OSER1-AS1, and illustrate how they affect NSCLC progression. OSER1-AS1 expression in NSCLC was measured by reverse transcription-quantitative polymerase chain reaction. Cell Counting Kit-8 assay, flow cytometry, cell migration and invasion assay, and tumor xenograft assay were performed to analyze the effects of OSER1-AS1 on the malignant phenotypes of NSCLC cells. Bioinformatics prediction with luciferase reporter and RNA immunoprecipitation assays were performed to determine the interaction between OSER1-AS1 and microRNA-433-3p (miR-433-3p). OSER1-AS1 was strongly expressed in NSCLC tissues and cell lines. Enhanced OSER1-AS1 expression was significantly correlated with tumor size, TNM stage, and lymph node metastasis in patients with NSCLC. Patients with NSCLC exhibiting high OSER1-AS1 expression had shorter overall survival than those exhibiting low OSER1-AS1 expression. Functionally, a reduction in OSER1-AS1 expression led to significant decreases in NSCLC cell proliferation, migration, and invasion as well as an increase in cell apoptosis in vivo. OSER1-AS1 knockdown suppressed the tumorigenic ability of NSCLC cells in vivo. Mechanistically, OSER1-AS1 acts as a competing endogenous RNA (ceRNA) in NSCLC cells by sponging miR-433-3p and thereby increasing the expression of mothers against decapentaplegic homolog 2 (Smad2). Finally, restoration experiments revealed that the suppression of miR-433-3p and restoration of Smad2 both counteracted the suppressive effects of OSER1-AS1 depletion in NSCLC cells. Our findings illustrate the biological importance of the OSER1-AS1/miR-433-3p/Smad2 pathway in NSCLC progression and offer a novel perspective regarding the identification of effective therapeutic and diagnostic targets.
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