Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis

MicroRNAs (miRNAs) are small noncoding RNA molecules that interact with target mRNAs at specific sites to induce cleavage of the mRNA or inhibit translation. Such miRNAs play a vital role in gene expression and in several other biological processes, including cell death. We have studied the mechanis...

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Main Authors: Akira Sato, Akihiro Yamamoto, Akira Shimotsuma, Yoko Ogino, Naoki Funayama, Yui Takahashi, Akiko Hiramoto, Yusuke Wataya, Hye‐Sook Kim
Format: Article
Language:English
Published: Wiley 2020-11-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.12995
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author Akira Sato
Akihiro Yamamoto
Akira Shimotsuma
Yoko Ogino
Naoki Funayama
Yui Takahashi
Akiko Hiramoto
Yusuke Wataya
Hye‐Sook Kim
author_facet Akira Sato
Akihiro Yamamoto
Akira Shimotsuma
Yoko Ogino
Naoki Funayama
Yui Takahashi
Akiko Hiramoto
Yusuke Wataya
Hye‐Sook Kim
author_sort Akira Sato
collection DOAJ
description MicroRNAs (miRNAs) are small noncoding RNA molecules that interact with target mRNAs at specific sites to induce cleavage of the mRNA or inhibit translation. Such miRNAs play a vital role in gene expression and in several other biological processes, including cell death. We have studied the mechanisms regulating cell death (necrosis in original F28‐7 cells and apoptosis in their variant F28‐7‐A cells) in the mouse mammary tumor cell line FM3A using the anticancer agent floxuridine (FUdR). We previously reported that inhibition of heat‐shock protein 90 by the specific inhibitor geldanamycin (GA) in F28‐7 cells causes a shift from necrosis to apoptosis. In this study, we investigated the intracellular miRNA expression profiles of FUdR‐treated F28‐7 cells (necrotic condition), GA plus FUdR‐treated F28‐7 cells (apoptotic condition), and FUdR‐treated F28‐7‐A cells (apoptotic condition) through miRNA microarray analysis. In addition, we knocked down Dicer, a key molecule for the expression of mature miRNAs, in F28‐7 cells to examine whether it modulates FUdR‐induced cell death. Our analysis revealed that the miRNA expression patterns differ significantly between these cell death conditions. Furthermore, we identified miRNA candidates that regulate cell death. Knockdown of Dicer in FUdR‐treated necrosis‐fated cells caused a partial shift from necrosis to apoptosis. These findings suggest that modulation of miRNA expression patterns influences the decision of cell death fate toward necrosis or apoptosis. Our findings may serve as a basis for further study of the functions of miRNAs in cell death mechanisms.
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spelling doaj.art-f4bfe96a07e94b6aaa2d75a58e4d96352022-12-22T03:00:17ZengWileyFEBS Open Bio2211-54632020-11-0110112417242610.1002/2211-5463.12995Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosisAkira Sato0Akihiro Yamamoto1Akira Shimotsuma2Yoko Ogino3Naoki Funayama4Yui Takahashi5Akiko Hiramoto6Yusuke Wataya7Hye‐Sook Kim8Department of Biochemistry Faculty of Pharmaceutical Sciences Tokyo University of Science Chiba JapanDivision of International Infectious Disease Control Faculty of Pharmaceutical Sciences Okayama University Okayama JapanDepartment of Biochemistry Faculty of Pharmaceutical Sciences Tokyo University of Science Chiba JapanDepartment of Biochemistry Faculty of Pharmaceutical Sciences Tokyo University of Science Chiba JapanDepartment of Biochemistry Faculty of Pharmaceutical Sciences Tokyo University of Science Chiba JapanDepartment of Biochemistry Faculty of Pharmaceutical Sciences Tokyo University of Science Chiba JapanDivision of International Infectious Disease Control Faculty of Pharmaceutical Sciences Okayama University Okayama JapanDivision of International Infectious Disease Control Faculty of Pharmaceutical Sciences Okayama University Okayama JapanDivision of International Infectious Disease Control Faculty of Pharmaceutical Sciences Okayama University Okayama JapanMicroRNAs (miRNAs) are small noncoding RNA molecules that interact with target mRNAs at specific sites to induce cleavage of the mRNA or inhibit translation. Such miRNAs play a vital role in gene expression and in several other biological processes, including cell death. We have studied the mechanisms regulating cell death (necrosis in original F28‐7 cells and apoptosis in their variant F28‐7‐A cells) in the mouse mammary tumor cell line FM3A using the anticancer agent floxuridine (FUdR). We previously reported that inhibition of heat‐shock protein 90 by the specific inhibitor geldanamycin (GA) in F28‐7 cells causes a shift from necrosis to apoptosis. In this study, we investigated the intracellular miRNA expression profiles of FUdR‐treated F28‐7 cells (necrotic condition), GA plus FUdR‐treated F28‐7 cells (apoptotic condition), and FUdR‐treated F28‐7‐A cells (apoptotic condition) through miRNA microarray analysis. In addition, we knocked down Dicer, a key molecule for the expression of mature miRNAs, in F28‐7 cells to examine whether it modulates FUdR‐induced cell death. Our analysis revealed that the miRNA expression patterns differ significantly between these cell death conditions. Furthermore, we identified miRNA candidates that regulate cell death. Knockdown of Dicer in FUdR‐treated necrosis‐fated cells caused a partial shift from necrosis to apoptosis. These findings suggest that modulation of miRNA expression patterns influences the decision of cell death fate toward necrosis or apoptosis. Our findings may serve as a basis for further study of the functions of miRNAs in cell death mechanisms.https://doi.org/10.1002/2211-5463.12995apoptosisdicerfloxuridinegeldanamycinmicroRNA expressionnecrosis
spellingShingle Akira Sato
Akihiro Yamamoto
Akira Shimotsuma
Yoko Ogino
Naoki Funayama
Yui Takahashi
Akiko Hiramoto
Yusuke Wataya
Hye‐Sook Kim
Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis
FEBS Open Bio
apoptosis
dicer
floxuridine
geldanamycin
microRNA expression
necrosis
title Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis
title_full Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis
title_fullStr Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis
title_full_unstemmed Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis
title_short Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis
title_sort intracellular microrna expression patterns influence cell death fates for both necrosis and apoptosis
topic apoptosis
dicer
floxuridine
geldanamycin
microRNA expression
necrosis
url https://doi.org/10.1002/2211-5463.12995
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