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.

Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer

“…Several recent studies have found that microRNAs (miRs) are involved in post-transcriptional downregulation of HDAC9. Specifically, HDAC9 has been found to be downregulated by miR-188 in bone marrow stromal cells [27], by miR-361-5p in cells associated with cardiac hypertrophy [28], by miR-936 or miR-101-3p in retinoblastoma cells [29,30], by miR-383-5p in gastric carcinoma cells [31], by miR-211-5p in bladder cancer cells [32], by miR-30d-5p in esophageal squamous cell carcinoma cells [33], by miR-509 3p in nonsmall cell lung cancer cells [34] and by miR-377 in oral squamous cell carcinoma cells [35].…”

“…HDAC9 is a direct target of miR5093p. It is, therefore, likely that the CBR3AS1/miR5093p/ HDAC9 pathway plays an important role in the development and progression of NSCLC [34].…”

The nomogram based on the 6-lncRNA model can promote the prognosis prediction of patients with breast invasive carcinoma

“…It was initially found to be highly expressed in prostate cancer (PCa) 30 and to interact with androgen receptor to promote PCa cell proliferation, migration and invasion, further leading to a reduced survival rate 31 . This lncRNA was also upregulated in hepatocellular carcinoma, gastric cancer, esophageal squamous cell carcinoma 32 , nonsmall cell lung cancer 33 , colon cancer 34 and glioma 35 and was associated with poor prognosis. In Xu's study 36 , CBR3-AS1 was found to be a cancer-promoting factor associated with a worse prognosis of breast cancer.…”

ChrXq27.3 miRNA cluster functions in cancer development

“…2 ) [ 93 ]. Moreover, miR-509-3p inhibits proliferation and increases apoptosis by targeting HDAC9 [ 39 ]. miR-509-3p also plays a role in treatment resistance by sensitizing ovarian cancer cells to cisplatin and olaparib by targeting XIAP , HMGA2, and RAD51 (Fig.…”