Lu Xiyi, Huang Chenjun, He Xuezhi, Liu Xinyin, Ji Jianmei, Zhang Erbao, Wang Wei, Guo Renhua
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of thoracic surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Cell Physiol Biochem. 2017;42(5):1857-1869. doi: 10.1159/000479543. Epub 2017 Jul 27.
In recent years, long non-coding RNAs (lncRNAs) have been shown to be a novel class of regulators of cancer biological processes. Although lncRNAs are dysregulated in numerous cancer types, limited data are available on the expression profiles and potential functions of lncRNAs in lung adenocarcinoma (LUAD). This study evaluated the expression and biological roles of lncRNA SOX21 antisense RNA 1 (SOX21-AS1) in LUAD.
Quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression levels of SOX21-AS1 in 68 pairs of LUAD tissues and corresponding non-tumor tissues. The effect of SOX21-AS1 on proliferation was evaluated by MTT, colony formation, EdU assays, flow-cytometric analysis and in vivo tumor formation assays. Real-time PCR, western-blot and immunohistochemistry were used to evaluate the mRNA and protein expression of p57.
Higher expression levels of SOX21-AS1 positively correlated with tumor size and advanced tumor-node-metastasis (TNM) stage. Multivariate analyses indicated that SOX21-AS1 expression could serve as an independent prognostic factor for overall survival of LUAD. Furthermore, knockdown of SOX21-AS1 significantly inhibited LUAD cell proliferation both in vitro and in vivo and induced cell cycle phase arrest and cell apoptosis. Importantly, through qRT-PCR and western blot analysis, we found that inhibition of SOX21-AS1 remarkably induced p57 expression.
Collectively, our study demonstrates that SOX21-AS1 is involved in the development and progression of LUAD and that SOX21-AS1 may be a potential diagnostic factor as well as a target for new therapies for patients with LUAD.
近年来，长链非编码RNA（lncRNAs）已被证明是癌症生物学过程的一类新型调节因子。尽管lncRNAs在多种癌症类型中表达失调，但关于lncRNAs在肺腺癌（LUAD）中的表达谱和潜在功能的数据有限。本研究评估了lncRNA SOX21反义RNA 1（SOX21-AS1）在LUAD中的表达及生物学作用。
采用定量逆转录PCR（qRT-PCR）检测68对LUAD组织及相应非肿瘤组织中SOX21-AS1的表达水平。通过MTT、集落形成、EdU检测、流式细胞术分析和体内肿瘤形成实验评估SOX21-AS1对增殖的影响。采用实时PCR、蛋白质免疫印迹和免疫组织化学评估p57的mRNA和蛋白表达。
SOX21-AS1的高表达水平与肿瘤大小和晚期肿瘤-淋巴结-转移（TNM）分期呈正相关。多因素分析表明，SOX21-AS1表达可作为LUAD总体生存的独立预后因素。此外，敲低SOX21-AS1在体外和体内均显著抑制LUAD细胞增殖，并诱导细胞周期阻滞和细胞凋亡。重要的是，通过qRT-PCR和蛋白质免疫印迹分析，我们发现抑制SOX21-AS1可显著诱导p57表达。
总体而言，我们的研究表明SOX21-AS1参与LUAD的发生和发展，且SOX21-AS1可能是LUAD患者的潜在诊断因子及新治疗靶点。
