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lncRNA相关ceRNA网络的综合分析揭示了lncRNA、miRNA和mRNA生物标志物在人直肠乙状结肠交界处癌中的新潜力。

Comprehensive analysis of lncRNA-associated ceRNA network reveals the novel potential of lncRNA, miRNA and mRNA biomarkers in human rectosigmoid junction cancer.

作者信息

Zhang Qianshi, Feng Zhen, Shi Shasha, Zhang Yu, Ren Shuangyi

机构信息

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.

Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.

出版信息

Oncol Lett. 2021 Feb;21(2):144. doi: 10.3892/ol.2020.12405. Epub 2020 Dec 21.

Abstract

Although accumulating evidence has confirmed the potential biological functions of long non-coding RNAs (lncRNAs) as competitive endogenous RNAs (ceRNAs) in colorectal tumorigenesis and progression, few studies have focused on rectosigmoid junction cancer. In the present study, a comprehensive analysis was conducted to explore lncRNA-mediated ceRNA implications and their potential value for prognosis. lncRNA, microRNA (miR/miRNA) and mRNA expression profiles were downloaded from The Cancer Genome Atlas database. Subsequently, a lncRNA-miRNA-mRNA regulatory network was constructed to evaluate the functions of these differentially expressed genes on overall survival (OS) for rectosigmoid junction cancer. As a result, a rectosigmoid junction cancer-specific ceRNA network was successfully constructed with 7 differentially expressed (DE)lncRNAs, 16 DEmiRNAs and 71 DEmRNAs. Among the network, one DElncRNA (small nucleolar RNA host gene 20) and three mRNAs (sodium- and chloride-dependent taurine transporter, fibroblast growth factor 13 and tubulin polyglutamylase TTLL7) were significantly associated with OS (P<0.05). Additionally, two lncRNAs (KCNQ1OT1 and MIR17HG) interacted with most of the DEmiRNAs. Notably, two top-ranked miRNAs (hsa-miR-374a-5p and hsa-miR-374b-5p) associated networks were identified to be markedly associated with the pathogenesis. Furthermore, four DEmRNAs (caveolin-1, MET, filamin-A and AKT3) were enriched in the Kyoto Encylopedia of Gene and Genomes pathway analysis, as well as being included in the ceRNA network. In summary, the present results revealed that a specific lncRNA-miRNA-mRNA network was associated with rectosigmoid junction cancer, providing several molecules that may be used as novel prognostic biomarkers and therapeutic targets.

摘要

尽管越来越多的证据证实了长链非编码RNA(lncRNA)作为竞争性内源性RNA(ceRNA)在结直肠癌发生和发展中的潜在生物学功能,但很少有研究关注直肠乙状结肠交界处癌。在本研究中,进行了全面分析以探索lncRNA介导的ceRNA影响及其对预后的潜在价值。lncRNA、微小RNA(miR/miRNA)和mRNA表达谱从癌症基因组图谱数据库下载。随后,构建了lncRNA-miRNA-mRNA调控网络,以评估这些差异表达基因对直肠乙状结肠交界处癌总生存期(OS)的作用。结果,成功构建了一个直肠乙状结肠交界处癌特异性ceRNA网络,其中包含7个差异表达(DE)lncRNA、16个DEmiRNA和71个DEmRNA。在该网络中,一个DElncRNA(小核仁RNA宿主基因20)和三个mRNA(钠和氯依赖性牛磺酸转运体、成纤维细胞生长因子13和微管蛋白多聚谷氨酰胺酶TTLL7)与OS显著相关(P<0.05)。此外,两个lncRNA(KCNQ1OT1和MIR17HG)与大多数DEmiRNA相互作用。值得注意的是,鉴定出两个排名靠前的miRNA(hsa-miR-374a-5p和hsa-miR-374b-5p)相关网络与发病机制显著相关。此外,四个DEmRNA(小窝蛋白-1、MET、细丝蛋白-A和AKT3)在京都基因与基因组百科全书通路分析中富集,并包含在ceRNA网络中。总之,本研究结果表明,一个特定的lncRNA-miRNA-mRNA网络与直肠乙状结肠交界处癌相关,提供了几个可能用作新型预后生物标志物和治疗靶点的分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e40a/7798100/7a26a801bcce/ol-21-02-12405-g00.jpg

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