MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival.

MicroRNA-224 (miR-224) is frequently over-expressed in liver and colorectal cancers. We and others have previously described the role of miR-224 over-expression in cell proliferation in vitro but we have yet to identify the relevant miR-224 direct target. In this study, we further demonstrated that...

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Autores principales: Yu Wang, Jianwei Ren, Yun Gao, Joel Z I Ma, Han Chong Toh, Pierce Chow, Alexander Y F Chung, London L P J Ooi, Caroline G L Lee
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/b02347caf191495fa33d49eaff6e98a5
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spelling oai:doaj.org-article:b02347caf191495fa33d49eaff6e98a52021-11-18T09:02:30ZMicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival.1932-620310.1371/journal.pone.0068744https://doaj.org/article/b02347caf191495fa33d49eaff6e98a52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23922662/?tool=EBIhttps://doaj.org/toc/1932-6203MicroRNA-224 (miR-224) is frequently over-expressed in liver and colorectal cancers. We and others have previously described the role of miR-224 over-expression in cell proliferation in vitro but we have yet to identify the relevant miR-224 direct target. In this study, we further demonstrated that miR-224 up-regulation promotes cell proliferation using both in vitro assays and in vivo tumor growth models. We systematically screened for high confidence miR-224 targets by overlapping in silico predicted targets from multiple algorithms and significantly down-regulated genes in miR-224-expressing cells from whole genome expression microarrays. A total of 72 high confidence miR-224 targets were identified and found to be enriched in various cancer-related processes. SMAD family member 4 (SMAD4) is experimentally validated as the direct cellular target through which miR-224 promotes cell proliferation. The clinical relevance of our experimental observations was supported by a statistically significant inverse correlation between miR-224 and SMAD4 transcript expression in tumor versus paired adjacent non-tumorous tissues from HCC patients (p<0.001, r= -0.45, R(2) =0.122). Furthermore, miR-224 up-regulation and SMAD4 down-regulation is significantly associated with poorer patient survival (p<0.05). In summary, miR-224/SMAD4 pathway is a clinically relevant pathway to provide new insights in understanding HCC. (191 words).Yu WangJianwei RenYun GaoJoel Z I MaHan Chong TohPierce ChowAlexander Y F ChungLondon L P J OoiCaroline G L LeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e68744 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yu Wang
Jianwei Ren
Yun Gao
Joel Z I Ma
Han Chong Toh
Pierce Chow
Alexander Y F Chung
London L P J Ooi
Caroline G L Lee
MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival.
description MicroRNA-224 (miR-224) is frequently over-expressed in liver and colorectal cancers. We and others have previously described the role of miR-224 over-expression in cell proliferation in vitro but we have yet to identify the relevant miR-224 direct target. In this study, we further demonstrated that miR-224 up-regulation promotes cell proliferation using both in vitro assays and in vivo tumor growth models. We systematically screened for high confidence miR-224 targets by overlapping in silico predicted targets from multiple algorithms and significantly down-regulated genes in miR-224-expressing cells from whole genome expression microarrays. A total of 72 high confidence miR-224 targets were identified and found to be enriched in various cancer-related processes. SMAD family member 4 (SMAD4) is experimentally validated as the direct cellular target through which miR-224 promotes cell proliferation. The clinical relevance of our experimental observations was supported by a statistically significant inverse correlation between miR-224 and SMAD4 transcript expression in tumor versus paired adjacent non-tumorous tissues from HCC patients (p<0.001, r= -0.45, R(2) =0.122). Furthermore, miR-224 up-regulation and SMAD4 down-regulation is significantly associated with poorer patient survival (p<0.05). In summary, miR-224/SMAD4 pathway is a clinically relevant pathway to provide new insights in understanding HCC. (191 words).
format article
author Yu Wang
Jianwei Ren
Yun Gao
Joel Z I Ma
Han Chong Toh
Pierce Chow
Alexander Y F Chung
London L P J Ooi
Caroline G L Lee
author_facet Yu Wang
Jianwei Ren
Yun Gao
Joel Z I Ma
Han Chong Toh
Pierce Chow
Alexander Y F Chung
London L P J Ooi
Caroline G L Lee
author_sort Yu Wang
title MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival.
title_short MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival.
title_full MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival.
title_fullStr MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival.
title_full_unstemmed MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival.
title_sort microrna-224 targets smad family member 4 to promote cell proliferation and negatively influence patient survival.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/b02347caf191495fa33d49eaff6e98a5
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