Key Genes and Regulatory Networks Involved in the Initiation, Progression and Invasion of Colorectal Cancer

Abstract

Aim:Until now, identification of drug targets for treatment of patients with specific stages of colorectal cancer (CRC) has remained a challenging field of research. Herein, we aimed to identify the key genes and regulatory networks involved in each stage of CRC.Results:The results of gene expression profiles were integrated with protein–protein interaction networks, and topologically analyzed. The most important regulatory genes (e.g., CDK1, UBC, ESR1 and ATXN1) and signaling pathways (e.g., Wnt, MAPK and JAK-STAT) in CRC initiation, progression and metastasis were identified. In vitro analysis confirmed some in silico findings.Conclusion:Our study introduces functional hub genes, subnetworks, prioritizes signaling pathways and novel biomarkers in CRC that may guide further development of targeted therapy programs.

SCAMP2/5 as diagnostic and prognostic markers for acute myeloid leukemia

“…Importantly, alterations in cytoskeletal pathways mediated by SCAMPs can affect cell–cell adhesion and may result in cell polarity loss and the increase of cell motility and invasion via changing components of the plasma membrane 5 , 8 – 10 . In consistent with these reports, dysregulation of SCAMPs has been found in series of human malignancies, such as hepatocellular carcinoma 11 , lung cancer 12 ; breast cancer 5 , colorectal cancer 2 , ovarian cancer 3 , pancreatic cancer and gallbladder cancer 6 , 13 . Recently, the role of SCAMPs in human cancers has been a topic of increasing interest.…”

“…The secretory carrier-associated membrane proteins (SCAMPs), a family of transcription factors encoded by five SCAMP genes in eukaryotes, are ubiquitously expressed in secretory membrane 1 . SCAMPs control intracellular trafficking and signaling involved in cell–cell adhesion, cancer migration and invasion 2 – 6 . Based on the variable presence of multiple N-terminal asparagine-proline-phenylalanine (NPF) repeats, human SCAMPs are divided into two groups: SCAMP1/2/3 (with NPF repeats) and SCAMP4/5 (without NPF repeats), whereas, SCAMPs with the same NPF repeats may have distinct functions.…”

MiR-125b-5p Is Involved in Sorafenib Resistance through Ataxin-1-Mediated Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

“…ATXN1 loss-of-function is implicated in cancer pathogenesis. In colorectal cancer, it has been reported that ATXN1 is a putative cancer gene and expression of ATXN1 in tumor cells is downregulated compared with normal colon cells [ 28 , 29 ]. However, the full spectrum of ATXN1 functions is far from being fully characterized.…”

Role of Stress-Survival Pathways and Transcriptomic Alterations in Progression of Colorectal Cancer: A Health Disparities Perspective

“…CRC is a multistep process that is described by a shift in the gene expression profile when the cell starts to evolve from the early to the late stage of CRC [ 52 ]. In this section, we focus on some of the genes that have been identified to be related to tumorigenesis and metastasis of CRC ( Table 1 ).…”

“…Tumor suppressor genes ( APC or TP53 ) and oncogenes ( KRAS or BRAF ) work together in apoptotic failure and progression of CRC [ 206 , 210 , 211 ]. These genes may sometimes also regulate sporadic and hereditary CRC [ 52 ]. Up to 70% of CRC cases show either mutation or deletion in tumor suppressor genes including TP53 [ 209 ].…”