Long noncoding RNA OSER1‑AS1 promotes the malignant properties of non‑small cell lung cancer by sponging microRNA‑433‑3p and thereby increasing Smad2 expression

Liu,Xinmei; Huang,Shasha; Guan,Yun; Zhang,Qing

doi:10.3892/or.2020.7645

Long noncoding RNA OSER1‑AS1 promotes the malignant properties of non‑small cell lung cancer by sponging microRNA‑433‑3p and thereby increasing Smad2 expression

Authors:
- Xinmei Liu
- Shasha Huang
- Yun Guan
- Qing Zhang
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Affiliations: Department of Respiratory Disease, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Department of General Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
Published online on: June 12, 2020 https://doi.org/10.3892/or.2020.7645
Pages: 599-610
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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