已发表论文

大肠癌(CRC)中的 BGN  和 COL11A1  调节网络分析表明 BGN  影响 CRC 细胞的生物学功能并与 miR-6828-5p 相互作用

 

Authors Chen D, Qin Y, Dai M, Li L, Liu H, Zhou Y, Qiu C, Chen Y, Jiang Y

Received 21 August 2020

Accepted for publication 19 November 2020

Published 22 December 2020 Volume 2020:12 Pages 13051—13069

DOI https://doi.org/10.2147/CMAR.S277261

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Yong Teng

Purpose: 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