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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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) |
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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 |
work_keys_str_mv |
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