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

Abstract

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.

The expression patterns and the prognostic roles of PTPN family members in digestive tract cancers

“…Another study illustrated that elevated PTPN3 expression promotes tumor recurrence and is detrimental to the prognosis of intrahepatic cholangiocarcinoma patients (28). Consistent with our results, Slattery ML et al (29) reported that PTPN11 expression is upregulated in CRC. PTPN11 was also suggested to impact the tumorigenesis and metastasis of CRC (30) and termed as a potential prognostic marker (31).…”

Role of MicroRNA-30c in cancer progression

“…In recent years, more and more studies have proved that miRNAs play important roles in a variety of cancer progression, such as respiratory cancers [4], digestive system cancers [5,6], neurological system cancers [7], genitourinary cancers [8] and vascular cancers [9]. miRNAs regulate the proliferation, differentiation, invasion, apoptosis and metastasis process of cancer cells in the form of oncogenes or tumor suppressor genes [10,11].It is worth noting that miRNAs and their target mRNA play synergistic network roles in cancer progression, and the analyses of miRNA expressions have identified potential markers for the diagnosis, prognosis and treatment of cancer patients [12,13].In these respects, more and more studies have confirmed…”

Expression and correlation of MALAT1 and SOX9 in non‐small cell lung cancer

“…In addition, it was found that the abnormal expression was related to many human disease and especially in tumours formation and development . SOX9 is over‐expressed in various cancers, such as colorectal cancer, prostate cancer, pancreatic cancer, lung cancer, brain cancer, and melanoma …”