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

Chunrui Zhang; Jing Jiang; Liqiang Wang; Liyu Zheng; Jiankai Xu; Xiaolin Qi; Huiying Huang; Jianping Lu; Kongning Li; Hong Wang

doi:10.3389/fgene.2020.00245

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

Front Genet. 2020 Mar 18:11:245. doi: 10.3389/fgene.2020.00245. eCollection 2020.

Authors

Chunrui Zhang^{1

2}, Jing Jiang³, Liqiang Wang¹, Liyu Zheng¹, Jiankai Xu¹, Xiaolin Qi⁴, Huiying Huang¹, Jianping Lu¹, Kongning Li^{1

4}, Hong Wang⁴

Affiliations

¹ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
² Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
³ Obstetrics and Gynecology Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁴ Key Laboratory of Tropical Translational Medicine of Ministry of Education and College of Biomedical Information and Engineering, Hainan Medical University, Haikou, China.

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 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.

Keywords: RNA-binding proteins; autophagy; biomarkers; colorectal cancer; regulatory network.