Long noncoding RNA CBR3 antisense RNA 1 promotes the aggressive phenotypes of non‑small‑cell lung cancer by sponging microRNA‑509‑3p and competitively upregulating HDAC9 expression

Guan,Yun; Yang,Juan; Liu,Xinmei; Chu,Lijuan

doi:10.3892/or.2020.7719

Long noncoding RNA CBR3 antisense RNA 1 promotes the aggressive phenotypes of non‑small‑cell lung cancer by sponging microRNA‑509‑3p and competitively upregulating HDAC9 expression

Authors:
- Yun Guan
- Juan Yang
- Xinmei Liu
- Lijuan Chu
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Affiliations: Department of Respiratory Medicine, 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: August 7, 2020 https://doi.org/10.3892/or.2020.7719
Pages: 1403-1414
Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long noncoding RNA CBR3 antisense RNA 1 (CBR3‑AS1) plays significant roles in the initiation and progression of osteosarcoma. The aim of the present study was to investigate the involvement of CBR3‑AS1 in the development of non‑small cell lung cancer (NSCLC). Reverse transcription‑quantitative PCR was performed to detect CBR3‑AS1 expression in NSCLC tissues and cell lines. The impacts of CBR3‑AS1 on cellular proliferation, apoptosis, migration and invasiveness in vitro, and tumor growth in vivo, were investigated using the Cell Counting Kit‑8 assay, flow cytometry, Transwell migration and invasion assays, and tumor xenograft model‑based analysis, respectively. The results indicated that CBR3‑AS1 was markedly upregulated in NSCLC tissues and cell lines. High CBR3‑AS1 expression was correlated with larger tumor size, advanced TNM stage, increased incidence of lymph node metastasis and shorter overall survival times in patients with NSCLC. Furthermore, CBR3‑AS1‑knockdown notably suppressed cellular proliferation, migration and invasiveness in vitro, and also promoted apoptosis and suppressed tumorigenicity in vivo. Mechanistic investigation demonstrated that CBR3‑AS1 functions as a competing endogenous RNA for microRNA‑509‑3p (miR‑509‑3p) in NSCLC cells. Furthermore, miR‑509‑3p exerted tumor‑suppressive effects in NSCLC, and histone deacetylase 9 (HDAC9) was identified as a direct target of miR‑509‑3p. HDAC9 expression was suppressed by CBR3‑AS1 depletion, which was abolished by miR‑509‑3p inhibition. Further rescue experiments revealed that increasing the output of the miR‑509‑3p/HDAC9 axis counteracted the CBR3‑AS1 depletion‑induced inhibitory effects on NSCLC cells. Collectively, the results of the present study indicate that the CBR3‑AS1/miR‑509‑3p/HDAC9 pathway exerts tumor‑promoting actions in NSCLC oncogenesis and progression, suggesting that this pathway is an effective target for the management of NSCLC.

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