Identification of Autophagy-Associated Biomarkers and Corresponding Regulatory Factors in the Progression of Colorectal Cancer

Abstract

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 RNAbinding 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 FDAapproved drugs were studied by a prognostic network. This would contribute to the identifications of new potential molecular therapeutic targets for CRC.The relationship between DEAGs expression level and patient survival was evaluated by the Cox regression analysis. Multivariate Cox regression analysis was used to fit the selected 2 www.broadinstitute.org/ccle 3

DDX17 promotes the growth and metastasis of lung adenocarcinoma

“…Overexpression of DDX17 enhances malignant migration and invasion of glioma cells by repressing beclin1 expression [ 29 ]. Zhang et al reported that DDX17 is important for the autophagy regulatory network through clinical data analyses of diverse stages for colorectal cancer [ 30 ]. Based on these reports, we investigated whether DDX17 regulates autophagy process in lung adenocarcinoma cells.…”

Measurement of Autophagy Activity Reveals Time-Dependent, Bacteria-Specific Turnover during Mycobacterium tuberculosis Infection

“…Promising results already exist in this regard where a defect in autophagy induction correlated with poor TB disease outcomes [ 72 ]. Supporting this notion, autophagy proteins (LC3B and p62) are currently being investigated as prognostic markers in cancer [ 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. After phagosomal damage, it is still unknown which M. tb proteins and phagosomal membrane proteins become ubiquitinated leading to autophagy activation.…”

Prediction of Prognostic Biomarkers and Construction of an Autophagy Prognostic Model for Colorectal Cancer Using Bioinformatics

“…Some RNA-binding proteins, such as DDX17, SETDB1, and POLR3, regulate autophagy in CRC by developing tumors and then searching for potential therapeutic targets in CRC. 11 Abnormal expression of NTF4 in CRC also affects autophagy. Knock-out of NTF4 prevents the transition of epithelial cells into mesenchyme in CRC and activates autophagy through the interaction of autophagy-related gene 5 (ATG5) with the mitogen-activated protein kinase pathway, thereby inhibiting the proliferation, migration, and invasion of the cells, along with clone-forming capacity, while promoting the arrest of cell cycle.…”