Yusuke Kanda1, Tokuichi Kawaguchi2, Mitsuhiko Osaki1,3, Kunishige Onuma1, Takahiro Ochiya4, Tomoyuki Kitagawa2, Futoshi Okada5,6. 1. Division of Pathological Biochemistry, Tottori University Faculty of Medicine, 86 Nishicho, Yonago, 683-8503, Japan. 2. Japanese Foundation for Cancer Research, Cancer Institute, Tokyo, 135-8550, Japan. 3. Chromosome Engineering Research Center, Tottori University, Yonago, 683-8503, Japan. 4. Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 5. Division of Pathological Biochemistry, Tottori University Faculty of Medicine, 86 Nishicho, Yonago, 683-8503, Japan. fuokada@med.tottori-u.ac.jp. 6. Chromosome Engineering Research Center, Tottori University, Yonago, 683-8503, Japan. fuokada@med.tottori-u.ac.jp.
Abstract
OBJECTIVE: In sporadic colon tumors, multistep process of well-known genetic alterations accelerates carcinogenesis; however, this does not appear to be the case in inflammation-related ones. We previously established a model of inflammation-related colon carcinogenesis using human colonic adenoma cells, and identified fascin as a driver gene of this process. We analyzed the microRNAs involved in the stable fascin expression in colon adenocarcinoma cells. MATERIALS AND METHODS: miRNA microarray analysis was performed using FPCK-1-1 adenoma cells and its-derived FPCKpP1-4 adenocarcinoma cells through chronic inflammation. To assess the involvement of miRNA in the inflammation-related carcinogenesis, sphere-forming ability, expression of colon cancer stemness markers, and stability of fascin protein via the proteasome using tough decoy RNA technique. RESULTS: We found that 17 miRNAs including miR-146a were upregulated and 16 miRNAs were downregulated in FPCKpP1-4 adenocarcinoma cells. We revealed that miR-146a in the adenocarcinoma cells brought about acquisition of sphere formation, cancer stemness, and inhibition of proteasomal degradation of the fascin protein. CONCLUSIONS: We found that stable fascin expression is brought about via the inhibition of proteasome degradation by miR-146a in the process of a chronic inflammation-related colon carcinogenesis.
OBJECTIVE: In sporadic colon tumors, multistep process of well-known genetic alterations accelerates carcinogenesis; however, this does not appear to be the case in inflammation-related ones. We previously established a model of inflammation-related colon carcinogenesis using humancolonic adenoma cells, and identified fascin as a driver gene of this process. We analyzed the microRNAs involved in the stable fascin expression in colon adenocarcinoma cells. MATERIALS AND METHODS: miRNA microarray analysis was performed using FPCK-1-1 adenoma cells and its-derived FPCKpP1-4 adenocarcinoma cells through chronic inflammation. To assess the involvement of miRNA in the inflammation-related carcinogenesis, sphere-forming ability, expression of colon cancer stemness markers, and stability of fascin protein via the proteasome using tough decoy RNA technique. RESULTS: We found that 17 miRNAs including miR-146a were upregulated and 16 miRNAs were downregulated in FPCKpP1-4 adenocarcinoma cells. We revealed that miR-146a in the adenocarcinoma cells brought about acquisition of sphere formation, cancer stemness, and inhibition of proteasomal degradation of the fascin protein. CONCLUSIONS: We found that stable fascin expression is brought about via the inhibition of proteasome degradation by miR-146a in the process of a chronic inflammation-related colon carcinogenesis.
Authors: S J Baker; A C Preisinger; J M Jessup; C Paraskeva; S Markowitz; J K Willson; S Hamilton; B Vogelstein Journal: Cancer Res Date: 1990-12-01 Impact factor: 12.701
Authors: Constance M Johnson; Caimiao Wei; Joe E Ensor; Derek J Smolenski; Christopher I Amos; Bernard Levin; Donald A Berry Journal: Cancer Causes Control Date: 2013-04-06 Impact factor: 2.506