c‐Src promotes tumor progression through downregulation of microRNA‐129‐1‐3p

MicroRNAs (miRNAs) fine‐tune cellular signaling by regulating expression of signaling proteins, and aberrant expression of miRNAs is observed in many cancers. The tyrosine kinase c‐Src is upregulated in various human cancers, but the molecular mechanisms underlying c‐Src‐mediated tumor progression r...

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Autores principales: Okuzaki, Daisuke, Yamauchi, Tomoe, Mitani, Fumie, Miyata, Mamiko, Ninomiya, Yuichi, Watanabe, Risayo, Akamatsu, Hiroki, Oneyama, Chitose
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004518/
https://www.ncbi.nlm.nih.gov/pubmed/31799727
http://dx.doi.org/10.1111/cas.14269
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author Okuzaki, Daisuke
Yamauchi, Tomoe
Mitani, Fumie
Miyata, Mamiko
Ninomiya, Yuichi
Watanabe, Risayo
Akamatsu, Hiroki
Oneyama, Chitose
author_facet Okuzaki, Daisuke
Yamauchi, Tomoe
Mitani, Fumie
Miyata, Mamiko
Ninomiya, Yuichi
Watanabe, Risayo
Akamatsu, Hiroki
Oneyama, Chitose
author_sort Okuzaki, Daisuke
collection PubMed
description MicroRNAs (miRNAs) fine‐tune cellular signaling by regulating expression of signaling proteins, and aberrant expression of miRNAs is observed in many cancers. The tyrosine kinase c‐Src is upregulated in various human cancers, but the molecular mechanisms underlying c‐Src‐mediated tumor progression remain unclear. In previous investigations of miRNA‐mediated control of c‐Src‐related oncogenic pathways, we identified miRNAs that were downregulated in association with c‐Src transformation and uncovered the signaling networks by predicting their target genes, which might act cooperatively to control tumor progression. Here, to further elucidate the process of cell transformation driven by c‐Src, we analyzed the expression profiles of miRNAs in a doxycycline‐inducible Src expression system. We found that miRNA (miR)‐129‐1‐3p was downregulated in the early phase of c‐Src‐induced cell transformation, and that reexpression of miR‐129‐1‐3p disrupted c‐Src‐induced cell transformation. In addition, miR‐129‐1‐3p downregulation was tightly associated with tumor progression in human colon cancer cells/tissues. Expression of miR‐129‐1‐3p in human colon cancer cells caused morphological changes and suppressed tumor growth, cell adhesion, and invasion. We also identified c‐Src and its critical substrate Fer, and c‐Yes, a member of the Src family of kinases, as novel targets of miR‐129‐1‐3p. Furthermore, we found that miR‐129‐1‐3p‐mediated regulation of c‐Src/Fer and c‐Yes is important for controlling cell adhesion and invasion. Downregulation of miR‐129‐1‐3p by early activation of c‐Src increases expression of these target genes and synergistically promotes c‐Src‐related oncogenic signaling. Thus, c‐Src‐miR‐129‐1‐3p circuits serve as critical triggers for tumor progression in many human cancers that harbor upregulation of c‐Src.
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spelling pubmed-70045182020-02-13 c‐Src promotes tumor progression through downregulation of microRNA‐129‐1‐3p Okuzaki, Daisuke Yamauchi, Tomoe Mitani, Fumie Miyata, Mamiko Ninomiya, Yuichi Watanabe, Risayo Akamatsu, Hiroki Oneyama, Chitose Cancer Sci Original Articles MicroRNAs (miRNAs) fine‐tune cellular signaling by regulating expression of signaling proteins, and aberrant expression of miRNAs is observed in many cancers. The tyrosine kinase c‐Src is upregulated in various human cancers, but the molecular mechanisms underlying c‐Src‐mediated tumor progression remain unclear. In previous investigations of miRNA‐mediated control of c‐Src‐related oncogenic pathways, we identified miRNAs that were downregulated in association with c‐Src transformation and uncovered the signaling networks by predicting their target genes, which might act cooperatively to control tumor progression. Here, to further elucidate the process of cell transformation driven by c‐Src, we analyzed the expression profiles of miRNAs in a doxycycline‐inducible Src expression system. We found that miRNA (miR)‐129‐1‐3p was downregulated in the early phase of c‐Src‐induced cell transformation, and that reexpression of miR‐129‐1‐3p disrupted c‐Src‐induced cell transformation. In addition, miR‐129‐1‐3p downregulation was tightly associated with tumor progression in human colon cancer cells/tissues. Expression of miR‐129‐1‐3p in human colon cancer cells caused morphological changes and suppressed tumor growth, cell adhesion, and invasion. We also identified c‐Src and its critical substrate Fer, and c‐Yes, a member of the Src family of kinases, as novel targets of miR‐129‐1‐3p. Furthermore, we found that miR‐129‐1‐3p‐mediated regulation of c‐Src/Fer and c‐Yes is important for controlling cell adhesion and invasion. Downregulation of miR‐129‐1‐3p by early activation of c‐Src increases expression of these target genes and synergistically promotes c‐Src‐related oncogenic signaling. Thus, c‐Src‐miR‐129‐1‐3p circuits serve as critical triggers for tumor progression in many human cancers that harbor upregulation of c‐Src. John Wiley and Sons Inc. 2020-01-17 2020-02 /pmc/articles/PMC7004518/ /pubmed/31799727 http://dx.doi.org/10.1111/cas.14269 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Okuzaki, Daisuke
Yamauchi, Tomoe
Mitani, Fumie
Miyata, Mamiko
Ninomiya, Yuichi
Watanabe, Risayo
Akamatsu, Hiroki
Oneyama, Chitose
c‐Src promotes tumor progression through downregulation of microRNA‐129‐1‐3p
title c‐Src promotes tumor progression through downregulation of microRNA‐129‐1‐3p
title_full c‐Src promotes tumor progression through downregulation of microRNA‐129‐1‐3p
title_fullStr c‐Src promotes tumor progression through downregulation of microRNA‐129‐1‐3p
title_full_unstemmed c‐Src promotes tumor progression through downregulation of microRNA‐129‐1‐3p
title_short c‐Src promotes tumor progression through downregulation of microRNA‐129‐1‐3p
title_sort c‐src promotes tumor progression through downregulation of microrna‐129‐1‐3p
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004518/
https://www.ncbi.nlm.nih.gov/pubmed/31799727
http://dx.doi.org/10.1111/cas.14269
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