Department of Respiratory Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian province, China.
Respiratory Medicine Center of Fujian Province, Quanzhou, 362000, Fujian province, China.
BMC Cancer. 2022 Feb 19;22(1):188. doi: 10.1186/s12885-022-09290-0.
Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involving in the tumorigenesis and metastasis of lung cancer. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD).
Totally, 1,955 DEmRNAs, 165 DEmiRNAs and 1,107 DElncRNAs were obtained in 10 paired normal and LUAD tissues. And a total of 8,912 paired lncRNA-miRNA-mRNA network was constructed. Using the Cancer Genome Atlas (TCGA) dataset, the module of ME turquoise was revealed to be most relevant to the progression of LUAD though Weighted Gene Co-expression Network Analysis (WGCNA).
Of the lncRNAs identified, LINC00639, RP4-676L2.1 and FENDRR were in ceRNA network established by our RNA-sequencing dataset. Using univariate Cox regression analysis, FENDRR was a risk factor of progression free survival (PFS) of stage I LUAD patients (HRs = 1.69, 95%CI 1.07-2.68, P < .050). Subsequently, diffe rential expression of FENDRR in paired normal and LUAD tissues was detected significant by real-time quantitative (qRT-PCR) (P < 0.001).
This study, for the first time, deciphered the regulatory role of FENDRR/miR-6815-5p axis in the progression of early-stage LUAD, which is needed to be established in vitro and in vivo.
越来越多的证据表明,长非编码 RNA(lncRNA)参与了肺癌的发生和转移。本研究旨在系统描述 lncRNA 相关竞争性内源 RNA(ceRNA)网络,并鉴定 I 期肺腺癌(LUAD)发生发展中的关键 lncRNA。
共从 10 对正常和 LUAD 组织中获得 1955 个差异表达 mRNA(DEmRNA)、165 个差异表达 miRNA(DEmiRNA)和 1107 个差异表达 lncRNA(DElncRNA)。构建了总共 8912 个 lncRNA-miRNA-mRNA 对网络。通过癌症基因组图谱(TCGA)数据集,加权基因共表达网络分析(WGCNA)显示 ME turquoise 模块与 LUAD 的进展最相关。
在鉴定的 lncRNA 中,LINC00639、RP4-676L2.1 和 FENDRR 存在于我们的 RNA-seq 数据集建立的 ceRNA 网络中。使用单变量 Cox 回归分析,FENDRR 是 I 期 LUAD 患者无进展生存期(PFS)的危险因素(HRs=1.69,95%CI 1.07-2.68,P<.050)。随后,通过实时定量(qRT-PCR)检测到 FENDRR 在配对的正常和 LUAD 组织中的差异表达具有统计学意义(P<.001)。
本研究首次揭示了 FENDRR/miR-6815-5p 轴在早期 LUAD 进展中的调控作用,需要在体外和体内进行验证。