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.

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.