ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation

MiRNAs are endogenous ~22 nt RNAs which play critical regulatory roles in a wide range of biological and pathological processes, which can act as oncogenes or tumor suppressor genes depending on their target genes. We have recently shown that ANXA1 inhibits the expression of miRNAs including miR196a...

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Main Authors: Yuan, Y., Anbalagan, D., Lee, L., Samy, R., Shanmugam, M., Kumar, Alan Prem, Sethi, G., Lobie, P., Lim, L.
Format: Journal Article
Published: Impact Journals LLC 2016
Online Access:http://hdl.handle.net/20.500.11937/62958
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author Yuan, Y.
Anbalagan, D.
Lee, L.
Samy, R.
Shanmugam, M.
Kumar, Alan Prem
Sethi, G.
Lobie, P.
Lim, L.
author_facet Yuan, Y.
Anbalagan, D.
Lee, L.
Samy, R.
Shanmugam, M.
Kumar, Alan Prem
Sethi, G.
Lobie, P.
Lim, L.
author_sort Yuan, Y.
building Curtin Institutional Repository
collection Online Access
description MiRNAs are endogenous ~22 nt RNAs which play critical regulatory roles in a wide range of biological and pathological processes, which can act as oncogenes or tumor suppressor genes depending on their target genes. We have recently shown that ANXA1 inhibits the expression of miRNAs including miR196a. Here, we show that miR196a was highly expressed in ER+ MCF-7 breast cancer cells when compared to normal mammary gland cells, with expression levels negatively correlating to ANXA1. ANXA1 inhibits the biogenesis of oncogenic miR-196a by suppressing primarymiR196a indirectly through the stimulation of c-myc and NFkB expression and activity in breast cancer cells. In a negative feedback loop, miR-196a directly inhibits ANXA1 and enhances breast cancer cell proliferation in vitro. Finally, miR196a promotes breast tumor growth in vivo. This study reports a novel regulatory circuit between ANXA1, NF-kB, c-myc and miR-196a which regulates breast cancer cell proliferation and tumor growth.
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institution Curtin University Malaysia
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publishDate 2016
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spelling curtin-20.500.11937-629582018-02-06T06:23:08Z ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation Yuan, Y. Anbalagan, D. Lee, L. Samy, R. Shanmugam, M. Kumar, Alan Prem Sethi, G. Lobie, P. Lim, L. MiRNAs are endogenous ~22 nt RNAs which play critical regulatory roles in a wide range of biological and pathological processes, which can act as oncogenes or tumor suppressor genes depending on their target genes. We have recently shown that ANXA1 inhibits the expression of miRNAs including miR196a. Here, we show that miR196a was highly expressed in ER+ MCF-7 breast cancer cells when compared to normal mammary gland cells, with expression levels negatively correlating to ANXA1. ANXA1 inhibits the biogenesis of oncogenic miR-196a by suppressing primarymiR196a indirectly through the stimulation of c-myc and NFkB expression and activity in breast cancer cells. In a negative feedback loop, miR-196a directly inhibits ANXA1 and enhances breast cancer cell proliferation in vitro. Finally, miR196a promotes breast tumor growth in vivo. This study reports a novel regulatory circuit between ANXA1, NF-kB, c-myc and miR-196a which regulates breast cancer cell proliferation and tumor growth. 2016 Journal Article http://hdl.handle.net/20.500.11937/62958 10.18632/oncotarget.8875 Impact Journals LLC unknown
spellingShingle Yuan, Y.
Anbalagan, D.
Lee, L.
Samy, R.
Shanmugam, M.
Kumar, Alan Prem
Sethi, G.
Lobie, P.
Lim, L.
ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation
title ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation
title_full ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation
title_fullStr ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation
title_full_unstemmed ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation
title_short ANXA1 inhibits miRNA-196a in a negative feedback loop through NF-kB and C-Myc to reduce breast cancer proliferation
title_sort anxa1 inhibits mirna-196a in a negative feedback loop through nf-kb and c-myc to reduce breast cancer proliferation
url http://hdl.handle.net/20.500.11937/62958