Ning Pengbo, Wu Zhongxing, Hu Aoxue, Li Xuepeng, He Jun, Gong Xiaocheng, Xia Yuqiong, Shang Yukui, Bian Huijie
School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, China.
Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi'an, Shaanxi, China.
PeerJ. 2018 Jan 12;6:e4254. doi: 10.7717/peerj.4254. eCollection 2018.
The etiology of cancer includes aberrant cellular homeostasis where a compromised RNA regulatory network is a prominent contributing factor. In particular, noncoding RNAs including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) were recently shown to play important roles in the initiation, progression, and metastasis of human cancers. Nonetheless, a mechanistic understanding of noncoding RNA functions in lung squamous cell carcinoma (LUSC) is lacking. To fill this critical gap in knowledge, we obtained mRNA, miRNA, and lncRNA expression data on patients with LUSC from the updated Cancer Genome Atlas (TCGA) database (2016). We successfully identified 3,366 mRNAs, 79 miRNAs, and 151 lncRNAs as key contributing factors of a high risk of LUSC. Furthermore, we hypothesized that the lncRNA-miRNA-mRNA regulatory axis positively correlates with LUSC and constructed a competitive endogenous RNA (ceRNA) network of LUSC by targeting interrelations with significantly aberrant expression data between miRNA and mRNA or lncRNA. Six ceRNAs (PLAU, miR-31-5p, miR-455-3p, FAM83A-AS1, MIR31HG, and MIR99AHG) significantly correlated with survival ( < 0.05). Finally, real-time quantitative PCR analysis showed that PLAU is significantly upregulated in SK-MES-1 cells compared with 16-BBE-T cells. Taken together, our findings represent new knowledge for a better understanding the ceRNA network in LUSC biology and pave the way to improved diagnosis and prognosis of LUSC.
癌症的病因包括细胞内稳态异常,其中受损的RNA调控网络是一个重要的促成因素。特别是,包括微小RNA(miRNA)和长链非编码RNA(lncRNA)在内的非编码RNA最近被证明在人类癌症的发生、发展和转移中发挥重要作用。然而,目前缺乏对非编码RNA在肺鳞状细胞癌(LUSC)中功能的机制性理解。为了填补这一关键的知识空白,我们从更新后的癌症基因组图谱(TCGA)数据库(2016年)中获取了LUSC患者的mRNA、miRNA和lncRNA表达数据。我们成功鉴定出3366个mRNA、79个miRNA和151个lncRNA是LUSC高风险的关键促成因素。此外,我们假设lncRNA-miRNA-mRNA调控轴与LUSC呈正相关,并通过针对miRNA与mRNA或lncRNA之间具有显著异常表达数据的相互关系构建了LUSC的竞争性内源RNA(ceRNA)网络。六个ceRNA(PLAU、miR-31-5p、miR-455-3p、FAM83A-AS1、MIR31HG和MIR99AHG)与生存率显著相关(<0.05)。最后,实时定量PCR分析表明,与16-BBE-T细胞相比,PLAU在SK-MES-1细胞中显著上调。综上所述,我们的研究结果为更好地理解LUSC生物学中的ceRNA网络提供了新知识,并为改善LUSC的诊断和预后铺平了道路。