Zhang Chunrui, Jiang Jing, Wang Liqiang, Zheng Liyu, Xu Jiankai, Qi Xiaolin, Huang Huiying, Lu Jianping, Li Kongning, Wang Hong
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Front Genet. 2020 Mar 18;11:245. doi: 10.3389/fgene.2020.00245. eCollection 2020.
Autophagy is a self-degradation process that maintains homeostasis against stress in cells. Autophagy dysfunction plays a central role in the development of tumors, such as colorectal cancer (CRC). In this study, autophagy-related differentially expressed genes, their downstream functions, and upstream regulatory factors including RNA-binding proteins (RBP) involved in programmed cell death in the CRC were investigated. Transcription factors (TFs) and miRNAs have been shown to mainly regulate autophagy genes. Interestingly, we found that some of the RBP in the CRC, such as DDX17, SETDB1, and POLR3A, play an important regulatory role in maintaining autophagy at a basal level during growth by acting as TFs that regulate autophagy. Promoter methylations showed negative regulations on differentially expressed autophagy gene (DEAG), while copy number variations revealed a positive role in them. A proportional hazards regression analysis indicated that using autophagy-related prognostic signature can divide patients into high-risk and low-risk groups. Autophagy associated FDA-approved drugs were studied by a prognostic network. This would contribute to the identifications of new potential molecular therapeutic targets for CRC.
自噬是一种自我降解过程，可维持细胞内应对应激的稳态。自噬功能障碍在肿瘤（如结直肠癌，CRC）的发生发展中起核心作用。在本研究中，我们调查了结直肠癌中自噬相关差异表达基因、其下游功能以及包括参与程序性细胞死亡的RNA结合蛋白（RBP）在内的上游调控因子。转录因子（TFs）和微小RNA（miRNAs）已被证明主要调节自噬基因。有趣的是，我们发现结直肠癌中的一些RBP，如DDX17、SETDB1和POLR3A，通过作为调节自噬的转录因子，在生长过程中维持基础水平的自噬方面发挥重要调节作用。启动子甲基化对差异表达的自噬基因（DEAG）显示出负调控作用，而拷贝数变异则显示出正调控作用。比例风险回归分析表明，使用自噬相关预后特征可将患者分为高风险和低风险组。通过预后网络研究了与自噬相关的FDA批准药物。这将有助于识别结直肠癌新的潜在分子治疗靶点。
