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miR - 452 - 5p在肺鳞状细胞癌中高表达的临床意义

Clinical significance of high expression of miR-452-5p in lung squamous cell carcinoma.

作者信息

Gan Xiao-Ning, Gan Ting-Qing, He Rong-Quan, Luo Jie, Tang Rui-Xue, Wang Han-Lin, Zhou Hong, Qing Hui, Ma Jie, Hu Xiao-Hua, Chen Gang

机构信息

Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

出版信息

Oncol Lett. 2018 May;15(5):6418-6430. doi: 10.3892/ol.2018.8088. Epub 2018 Feb 20.

Abstract

The role of microRNA (miRNA)-452-5p in lung squamous cell carcinoma (LUSC) remains unclear. Therefore, the present systematic study was performed to investigate the clinical significance and the rudimentary mechanism of the function of miR-452-5p in LUSC. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to confirm the expression level and clinical value of miR-452-5p in LUSC. Using online databases and bioinformatic software, gene ontology (GO), pathway and protein-protein interaction (PPI) analyses of miR-452-5p target genes were performed to examine the molecular mechanism of miR-452-5p. The association between the expression of miR-452-5p and that of its hub genes was verified using TCGA. Based on TCGA data on 387 clinical specimens, the expression of miR-452-5p in LUSC was significantly increased compared with adjacent lung tissues (7.1525±1.39063 vs. 6.0885±0.35298; P<0.001). The expression levels of miR-452-5p were significantly correlated with age (P=0.001) and tumor-node metastasis stage (P=0.028). Furthermore, the increased expression of miR-452-5p in LUSC compared with non-cancerous tissue [standard mean deviation (SMD), 0.372; 95% confidence interval (CI), 0.020-0.724; z=2.07; P=0.038] was validated by a meta-analysis of 720 clinical samples. The GO and pathway analyses revealed that miR-452-5p target genes were mainly enriched in the 'regulation of transcription', 'nucleoplasm', 'protein binding' and 'cell cycle' pathways. A total of 10 hub genes were identified by PPI analysis, and 5 hub genes (SMAD4, SMAD2, CDKN1B, YWHAE and YWHAB) were significantly enriched in the 'cell cycle' pathway. The expression of CDKN1B was negatively correlated with miR-452-5p (P=0.003). It was concluded that miR-452-5p may serve an essential role in the occurrence and progression of LUSC by targeting CDKN1B, which is involved in the cell cycle.

摘要

微小RNA(miRNA)-452-5p在肺鳞状细胞癌(LUSC)中的作用仍不清楚。因此,本研究进行了系统研究,以探讨miR-452-5p在LUSC中的临床意义及功能的基本机制。利用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)来确认miR-452-5p在LUSC中的表达水平和临床价值。使用在线数据库和生物信息学软件,对miR-452-5p靶基因进行基因本体(GO)、通路和蛋白质-蛋白质相互作用(PPI)分析,以研究miR-452-5p的分子机制。利用TCGA验证了miR-452-5p与其枢纽基因表达之间的关联。基于387份临床标本的TCGA数据,LUSC中miR-452-5p的表达与相邻肺组织相比显著升高(7.1525±1.39063对6.0885±0.35298;P<0.001)。miR-452-5p的表达水平与年龄(P=0.001)和肿瘤-淋巴结转移分期(P=0.028)显著相关。此外,通过对720份临床样本的荟萃分析验证了LUSC中miR-452-5p与非癌组织相比表达增加[标准平均差(SMD),0.372;95%置信区间(CI),0.020-0.724;z=2.07;P=0.038]。GO和通路分析显示,miR-452-5p靶基因主要富集于“转录调控”、“核质”、“蛋白质结合”和“细胞周期”通路。通过PPI分析共鉴定出10个枢纽基因,其中5个枢纽基因(SMAD4、SMAD2、CDKN1B、YWHAE和YWHAB)在“细胞周期”通路中显著富集。CDKN1B的表达与miR-452-5p呈负相关(P=0.003)。研究得出结论,miR-452-5p可能通过靶向参与细胞周期的CDKN1B在LUSC的发生和发展中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a246/5876433/3a572007426c/ol-15-05-6418-g00.jpg

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