Zhang Yu, Luo Jie, Wang Xiao, Wang Han-Lin, Zhang Xiu-Ling, Gan Ting-Qing, Chen Gang, Luo Dian-Zhong
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Oncol Lett. 2018 May;15(5):6147-6160. doi: 10.3892/ol.2018.8105. Epub 2018 Feb 22.
Long non-coding RNA HOXA11 antisense RNA (HOXA11-AS) has been previously reported to be involved in the tumorigenesis and progression of ovarian cancer and glioma. However, the function of HOXA11-AS in lung cancer remains unclear. Following the knockdown of HOXA11-AS in A549 cells, a microarray analysis was performed in order to detect the differences in microRNA (miRNA/miR) profiles. Subsequently, miR-642b-3p was selected for further analysis. Four miRNA target prediction algorithms were used to identify potential target genes of miR-642b-3p. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes, protein-protein interactions (PPIs) and network analysis, were performed to investigate the potential functions, pathways and networks of the target genes. Furthermore, the differential expression of miR-642b-3p and its target genes between normal lung and non-small cell lung cancer (NSCLC) tissues was verified using The Cancer Genome Atlas (TCGA) database. Six target genes [zinc finger protein 350, heterogeneous nuclear ribonucleoprotein U, high mobility group box 1, phosphodiesterase 4D (PDE4D), synaptotagmin binding cytoplasmic RNA interacting protein and basic helix-loop-helix family member B9] of miR-642b-3p were predicted using all 4 algorithms. It was revealed that miR-642b-3p was overexpressed in adenocarcinoma and squamous cell carcinoma tissues compared with non-cancerous lung tissues based on the TCGA database. From the 6 target genes, PDE4D was downregulated in lung adenocarcinoma and squamous cell carcinoma tissues, and a weak negative correlation between HOXA11-AS and PDE4D was identified. The area under the curve of PDE4D was 0.905 [95% confidence interval (CI), 0.879-0.931] for patients with lung adenocarcinoma and 0.665 (95% CI, 0.606-0.725) for patients with squamous cell carcinoma. Additionally, GO analysis of the target genes revealed that miR-642b-3p was specifically involved in complex cellular pathways. The target gene RAN binding protein 2 possessed the highest degree of interactions in the PPI network (degree=40). It was hypothesized that HOXA11-AS may have a function in NSCLC by regulating the expression of miR-642b-3p and PDE4D, which laid the foundation for the further elucidation of the potential molecular mechanisms of NSCLC.
长链非编码RNA HOXA11反义RNA（HOXA11-AS）此前已被报道参与卵巢癌和神经胶质瘤的肿瘤发生及进展。然而，HOXA11-AS在肺癌中的功能仍不清楚。在A549细胞中敲低HOXA11-AS后，进行了微阵列分析以检测微小RNA（miRNA/miR）谱的差异。随后，选择miR-642b-3p进行进一步分析。使用四种miRNA靶标预测算法来鉴定miR-642b-3p的潜在靶基因。进行了生物信息学分析，包括基因本体论（GO）、京都基因与基因组百科全书、蛋白质-蛋白质相互作用（PPI）和网络分析，以研究靶基因的潜在功能、途径和网络。此外，使用癌症基因组图谱（TCGA）数据库验证了miR-642b-3p及其靶基因在正常肺组织和非小细胞肺癌（NSCLC）组织之间的差异表达。使用所有4种算法预测了miR-642b-3p的6个靶基因[锌指蛋白350、不均一核核糖核蛋白U、高迁移率族蛋白盒1、磷酸二酯酶4D（PDE4D）、突触结合蛋白结合胞质RNA相互作用蛋白和碱性螺旋-环-螺旋家族成员B9]。基于TCGA数据库显示，与非癌性肺组织相比，miR-642b-3p在腺癌和鳞状细胞癌组织中过表达。在这6个靶基因中，PDE4D在肺腺癌和鳞状细胞癌组织中下调，并且鉴定出HOXA11-AS与PDE4D之间存在弱负相关。肺腺癌患者中PDE4D的曲线下面积为0.905[95%置信区间（CI），0.879-0.931]，鳞状细胞癌患者中为0.665（95%CI，0.606-0.725）。此外，对靶基因的GO分析表明，miR-642b-3p特别参与复杂的细胞途径。靶基因RAN结合蛋白2在PPI网络中具有最高的相互作用度（度=40）。据推测，HOXA11-AS可能通过调节miR-642b-3p和PDE4D的表达在NSCLC中发挥作用，这为进一步阐明NSCLC的潜在分子机制奠定了基础。
