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Published in: Inflammation Research 10/2018

01-10-2018 | Original Research Paper

Fascin protein stabilization by miR-146a implicated in the process of a chronic inflammation-related colon carcinogenesis model

Authors: Yusuke Kanda, Tokuichi Kawaguchi, Mitsuhiko Osaki, Kunishige Onuma, Takahiro Ochiya, Tomoyuki Kitagawa, Futoshi Okada

Published in: Inflammation Research | Issue 10/2018

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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.
Appendix
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Metadata
Title
Fascin protein stabilization by miR-146a implicated in the process of a chronic inflammation-related colon carcinogenesis model
Authors
Yusuke Kanda
Tokuichi Kawaguchi
Mitsuhiko Osaki
Kunishige Onuma
Takahiro Ochiya
Tomoyuki Kitagawa
Futoshi Okada
Publication date
01-10-2018
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 10/2018
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-018-1175-2

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