Systemic Chromosome Instability Resulted in Colonic Transcriptomic Changes in Metabolic, Proliferation, and Stem Cell Regulators in Sgo1-/+ Mice

Cancer Research
Chinthalapally V RaoHiroshi Y Yamada

Abstract

Colon cancer is the second most lethal cancer and is predicted to claim 49,700 lives in the United States this year. Chromosome instability (CIN) is observed in 80% to 90% of colon cancers and is thought to contribute to colon cancer progression and recurrence. To investigate the impact of CIN on colon cancer development, we developed shugoshin-1 (Sgo1) haploinsufficient (-/+) mice, an animal model focusing on mitotic error-induced CIN. In this study, we analyzed signature changes in the colonic transcriptome of Sgo1(-/+) mice to examine the molecular events underlying the altered carcinogenesis profiles in Sgo1(-/+) mice. We performed next-generation sequencing of normal-looking colonic mucosal tissue from mice treated with the carcinogen azoxymethane after 24 weeks. Transcriptome profiling revealed 349 hits with a 2-fold expression difference threshold (217 upregulated genes, 132 downregulated genes, P < 0.05). Pathway analyses indicated that the Sgo1-CIN tissues upregulated pathways known to be activated in colon cancer, including lipid metabolism (z score 4.47), Notch signaling (4.47), insulin signaling (3.81), and PPAR pathways (3.75), and downregulated pathways involved in immune responses including allograft rejection (6...Continue Reading

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Citations

Aug 18, 2016·Molecular Carcinogenesis·Chinthalapally V RaoHiroshi Y Yamada
Nov 14, 2016·Carcinogenesis·Chinthalapally V RaoHiroshi Y Yamada
Jun 28, 2019·Cell Cycle·Rita BrásLuís Pedro Resende
Oct 3, 2019·Experimental Biology and Medicine·Shirley Jusino, Harold I Saavedra
Aug 14, 2019·Current Colorectal Cancer Reports·Rachel E BrownChristopher S Williams

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