COL1A1 and MZB1 as the hub genes influenced the proliferation, invasion, migration and apoptosis of rectum adenocarcinoma cells by weighted correlation network analysis

Bioorg Chem. 2020 Jan:95:103457. doi: 10.1016/j.bioorg.2019.103457. Epub 2019 Dec 6.

Abstract

Objectives: The influences of COL1A1 and MZB1 on the proliferation, migration, invasion and apoptosis abilities of rectum adenocarcinoma was aimed to explore in this study.

Methods: Gene expression levels in rectum adenocarcinoma and adjacent tissues were analyzed by differential analysis. Weighted gene correlation network analysis (WGCNA) was employed to investigate rectal adenocarcinoma (READ) hub genes. MCODE was performed to screen the modules of protein-protein interaction network in Cytoscape software. Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool is considered to be the most effective tool in gene ontology (GO) enrichment and Kyoto Gene and Genomics Encyclopedia (KEGG) pathway analysis. Survival analysis was performed using READ patient information from TCGA-READ project database. Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) and western blot were employedto examinemRNA and protein expressions of COL1A1 and MZB1 in tumor tissues and cell lines. After transfecting various interference sequences by liposome-mediated transfection, the influence of COL1A1 and MZB1 on the proliferation, apoptosis, migration and invasion of rectal cancer cells were observed by plate clone formation assay, flow cytometry, wound healing assay and transwell assay respectively. Moreover, xenograft tumor growth assay in vivo validated the results.

Results: Higher expression levels of COL1A1 and lower expression levels of MZB1 were discovered in tumor tissues of patients with colorectal adenocarcinoma. Overexpression of MZB1 and silencing COL1A1 significantly inhibited proliferation, migration and invasion, while cell apoptosis was promoted. Overexpression of MZB1 and silencing COL1A1 inhibited the orthotopic growth of tumor in vivo.

Conclusion: COL1A1 promoted proliferation, migration and invasion but inhibited apoptosis of rectal adenocarcinoma cells while MZB1 was totally on the contrary.

Keywords: COL1A1; Hub gene; MZB1; Rectum adenocarcinoma; WGCNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adenocarcinoma
  • Apoptosis / genetics*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Collagen Type I / genetics*
  • Collagen Type I, alpha 1 Chain
  • Humans
  • Rectal Neoplasms
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • MZB1 protein, human