RGD Reference Report - The co-regulatory networks of tumor suppressor genes, oncogenes, and miRNAs in colorectal cancer. - Rat Genome Database

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The co-regulatory networks of tumor suppressor genes, oncogenes, and miRNAs in colorectal cancer.

Authors: Slattery, Martha L  Herrick, Jennifer S  Mullany, Lila E  Samowitz, Wade S  Sevens, John R  Sakoda, Lori  Wolff, Roger K 
Citation: Slattery ML, etal., Genes Chromosomes Cancer. 2017 Nov;56(11):769-787. doi: 10.1002/gcc.22481. Epub 2017 Jul 30.
RGD ID: 150524297
Pubmed: PMID:28675510   (View Abstract at PubMed)
PMCID: PMC5597468   (View Article at PubMed Central)
DOI: DOI:10.1002/gcc.22481   (Journal Full-text)

Tumor suppressor genes (TSGs) and oncogenes (OG) are involved in carcinogenesis. MiRNAs also contribute to cellular pathways leading to cancer. We use data from 217 colorectal cancer (CRC) cases to evaluate differences in TSGs and OGs expression between paired CRC and normal mucosa and evaluate how TSGs and OGs are associated with miRNAs. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were used. We focus on genes most strongly associated with CRC (fold change (FC) of >=1.5 or <=0.67) that were statistically significant after adjustment for multiple comparisons. Of the 74 TSGs evaluated, 22 were associated with carcinoma/normal mucosa differential expression. Ten TSGs were up-regulated (FAM123B, RB1, TP53, RUNX1, MSH2, BRCA1, BRCA2, SOX9, NPM1, and RNF43); six TSGs were down-regulated (PAX5, IZKF1, GATA3, PRDM1, TET2, and CYLD); four were associated with MSI tumors (MLH1, PTCH1, and CEBPA down-regulated and MSH6 up-regulated); and two were associated with MSS tumors (PHF6 and ASXL1 up-regulated). Thirteen of these TSGs were associated with 44 miRNAs. Twenty-seven of the 59 OGs evaluated were dysregulated: 14 down-regulated (KLF4, BCL2, SSETBP1, FGFR2, TSHR, MPL, KIT, PDGFRA, GNA11, GATA2, FGFR3, AR, CSF1R, and JAK3), seven up-regulated (DNMT1, EZH2, PTPN11, SKP2, CCND1, MET, and MYC); three down-regulated for MSI (FLT3, CARD11, and ALK); two up-regulated for MSI (IDH2 and HRAS); and one up-regulated with MSS tumors (CTNNB1). These findings suggest possible co-regulatory function between TSGs, OGs, and miRNAs, involving both direct and indirect associations that operate through feedback and feedforward loops.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colorectal cancer  IEP 150524297mRNA:increased expression:colorectal mucosa (human)RGD 
colorectal cancer  ISOAMER1 (Homo sapiens)150524297; 150524297mRNA:increased expression:colorectal mucosa (human)RGD 
colorectal carcinoma  IEP 150524297mRNA:decreased expression:colorectal mucosa (human)RGD 
colorectal carcinoma  ISOCSF1R (Homo sapiens)150524297; 150524297mRNA:decreased expression:colorectal mucosa (human)RGD 
colorectal carcinoma  IEP 150524297mRNA:increased expression:colorectal mucosa (human)RGD 
colorectal carcinoma  ISOPHF6 (Homo sapiens)150524297; 150524297mRNA:increased expression:colorectal mucosa (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Amer1  (APC membrane recruitment protein 1)
Csf1r  (colony stimulating factor 1 receptor)
Phf6  (PHD finger protein 6)

Genes (Mus musculus)
Amer1  (APC membrane recruitment 1)
Csf1r  (colony stimulating factor 1 receptor)
Phf6  (PHD finger protein 6)

Genes (Homo sapiens)
AMER1  (APC membrane recruitment protein 1)
CSF1R  (colony stimulating factor 1 receptor)
PHF6  (PHD finger protein 6)


Additional Information