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结直肠癌中与mA相关基因的表达模式及预后价值

Expression patterns and prognostic value of mA-related genes in colorectal cancer.

作者信息

Liu Xin, Liu Liwen, Dong Zihui, Li Jianhao, Yu Yan, Chen Xiaolong, Ren Fang, Cui Guangying, Sun Ranran

机构信息

Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.

Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.

出版信息

Am J Transl Res. 2019 Jul 15;11(7):3972-3991. eCollection 2019.

Abstract

Colorectal cancer (CRC), including colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ), is one of the most prevalent malignancies worldwide. N-methyladenosine (mA) is a ubiquitous RNA modification that plays a vital role in human tumors, but its expression patterns and prognostic value in CRC have not yet been determined. Here, we first used the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the Human Protein Atlas (HPA) databases and a tissue microarray (TMA) cohort to verify the expression of mA-related genes at the mRNA and protein levels. We found that most mA-related genes were substantially upregulated in tumor tissues compared with normal tissues, but METTL14, YTHDF3 and ALKBH5 were downregulated in CRC. There was no obvious difference in FTO. In addition, WTAP, METTL16, HNRNPC and YTHDC1 were abundantly expressed in COAD but not in READ. Moreover, immunofluorescence (IF) analyses of SW480 and HCT116 cells showed that most of the mA-related proteins were expressed in the nucleus and cytoplasm. Survival analysis demonstrated that the expression levels of METTL3, METTL14, METTL16, FTO and ALKBH5 were associated with the clinical outcomes of CRC patients. Taken together, all the results revealed that mA-related genes were dysregulated in CRC and might play a significant role in the progression of CRC.

摘要

结直肠癌(CRC),包括结肠腺癌(COAD)和直肠腺癌(READ),是全球最常见的恶性肿瘤之一。N-甲基腺苷(mA)是一种普遍存在的RNA修饰,在人类肿瘤中起着至关重要的作用,但其在结直肠癌中的表达模式和预后价值尚未确定。在此,我们首先使用癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)和人类蛋白质图谱(HPA)数据库以及一个组织微阵列(TMA)队列,在mRNA和蛋白质水平验证mA相关基因的表达。我们发现,与正常组织相比,大多数mA相关基因在肿瘤组织中显著上调,但METTL14、YTHDF3和ALKBH5在结直肠癌中下调。FTO没有明显差异。此外,WTAP、METTL16、HNRNPC和YTHDC1在COAD中大量表达,但在READ中不表达。此外,对SW480和HCT116细胞的免疫荧光(IF)分析表明,大多数mA相关蛋白在细胞核和细胞质中表达。生存分析表明,METTL3、METTL14、METTL16、FTO和ALKBH5的表达水平与结直肠癌患者的临床结局相关。综上所述,所有结果表明,mA相关基因在结直肠癌中失调,可能在结直肠癌的进展中起重要作用。

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