BGN and COL11A1 Regulatory Network Analysis in Colorectal Cancer (CRC) Reveals That BGN Influences CRC Cell Biological Functions and Interacts with miR-6828-5p

Danqi Chen,1 Ying Qin,2 Mengmeng Dai,1 Lulu Li,1 Hongpeng Liu,2 Yaoyao Zhou,3 Cheng Qiu,3 Yan Chen,1 Yuyang Jiang1,4 1State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Shenzhen, Guangdong, People’s Republic of China; 2Department of Gastrointestinal Surgery, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 3National & Local United Engineering Laboratory for Personalized Anti-Tumor Drugs, Shenzhen Kivita Innovative Drug Discovery Institute, Tsinghua Shenzhen International Graduate School, Shenzhen, Guangdong, People’s Republic of China; 4School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, People’s Republic of ChinaCorrespondence: Yan Chen; Yuyang Jiang Tel/Fax +86-755-26036017Email yanchen16@mails.tsinghua.edu.cn; jiangyy@sz.tsinghua.edu.cnPurpose: We explored specific expression profiles of BGN and COL11A1 genes and studied their biological functions in CRC using bioinformatics tools.Patients and Methods: A total of 68 pairs of cancer and non-cancerous tissues from CRC patients were enrolled in this study. Methods we used in this articles including: qRT-PCR, Western blot analysis, ELISA, GO and KEGG regulatory network analysis, tumor infiltration, luciferase reporter-based protein and etc.Results: According to The Cancer Genome Atlas (TCGA) data, BGN and COL11A1 expression levels were significantly higher in CRC patient samples than in samples from healthy controls. Moreover, levels were much higher in late-stage CRC than in early-stage disease, warranting evaluation of these genes as CRC prognostic biomarkers. Subsequently, qRT-PCR, Western blot analysis, and ELISA results obtained from analyses of CRC cells, tissues, and patient sera aligned with TCGA results. GO and KEGG regulatory network analysis revealed BGN- and COL11A1-associated genes that were functionally related to extracellular matrix (ECM) receptor pathway activation, with transcription factor genes RELA and NFKB1 positively associated with BGN expression and CEBPZ and SIRT1 with COL11A1 expression. Meanwhile, BGN and COL11A1 expression were separately and significantly correlated to tumor infiltration by six immune cell types. Additionally, kinase genes PLK1 and LYN appeared to be downstream targets of differentially expressed BGN and COL11A1, respectively. In addition, the expression of PLK1 mRNA was down-regulated while BGN was down-regulated. Finally, BGN effects on CRC cell proliferation, cycle, apoptosis, invasion, and migration were studied using molecular biological methods, including luciferase reporter-based protein analysis, qRT-PCR, and Western blot results, which revealed that miR-6828-5p may regulate BGN expression.Conclusion: We speculate that the use of BGN and COL11A1 as CRC biomarkers would improve CRC staging, while also providing several novel targets for use in the development of more effective CRC treatments.Keywords: colorectal cancer, COL11A1, BGN, PLK-1, miR-6828-5p