MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2.
<h4>Background</h4>Previous work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targe...
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oai:doaj.org-article:812b9e64a52f4f2bba2515035729fe432021-11-25T06:24:34ZMicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2.1932-620310.1371/journal.pone.0010147https://doaj.org/article/812b9e64a52f4f2bba2515035729fe432010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20418948/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Previous work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targets of let-7a, and if let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2.<h4>Methodology/principal</h4>Findings Real-time RT-PCR demonstrated that decreased levels of let-7a are present in resected prostate cancer samples and prostate cancer cell lines. Cellular proliferation was inhibited in PC3 cells and LNCaP cells after transfection with let-7a. Cell cycle analysis showed that let-7a induced cell cycle arrest at the G1/S phase. A dual-luciferase reporter assay demonstrated that the 3'UTR of E2F2 and CCND2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of E2F2 and CCND2. Our xenograft models of prostate cancer confirmed the capability of let-7a to inhibit prostate tumor development in vivo.<h4>Conclusions/significance</h4>These findings help to unravel the anti-proliferative mechanisms of let-7a in prostate cancer. Let-7a may also be novel therapeutic candidate for prostate cancer given its ability to induce cell-cycle arrest and inhibit cell growth, especially in hormone-refractory prostate cancer.Qingchuan DongPing MengTao WangWeiwei QinWeijun QinFuli WangJianlin YuanZhinan ChenAngang YangHe WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e10147 (2010) |
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Medicine R Science Q Qingchuan Dong Ping Meng Tao Wang Weiwei Qin Weijun Qin Fuli Wang Jianlin Yuan Zhinan Chen Angang Yang He Wang MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. |
description |
<h4>Background</h4>Previous work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targets of let-7a, and if let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2.<h4>Methodology/principal</h4>Findings Real-time RT-PCR demonstrated that decreased levels of let-7a are present in resected prostate cancer samples and prostate cancer cell lines. Cellular proliferation was inhibited in PC3 cells and LNCaP cells after transfection with let-7a. Cell cycle analysis showed that let-7a induced cell cycle arrest at the G1/S phase. A dual-luciferase reporter assay demonstrated that the 3'UTR of E2F2 and CCND2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of E2F2 and CCND2. Our xenograft models of prostate cancer confirmed the capability of let-7a to inhibit prostate tumor development in vivo.<h4>Conclusions/significance</h4>These findings help to unravel the anti-proliferative mechanisms of let-7a in prostate cancer. Let-7a may also be novel therapeutic candidate for prostate cancer given its ability to induce cell-cycle arrest and inhibit cell growth, especially in hormone-refractory prostate cancer. |
format |
article |
author |
Qingchuan Dong Ping Meng Tao Wang Weiwei Qin Weijun Qin Fuli Wang Jianlin Yuan Zhinan Chen Angang Yang He Wang |
author_facet |
Qingchuan Dong Ping Meng Tao Wang Weiwei Qin Weijun Qin Fuli Wang Jianlin Yuan Zhinan Chen Angang Yang He Wang |
author_sort |
Qingchuan Dong |
title |
MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. |
title_short |
MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. |
title_full |
MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. |
title_fullStr |
MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. |
title_full_unstemmed |
MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. |
title_sort |
microrna let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting e2f2 and ccnd2. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doaj.org/article/812b9e64a52f4f2bba2515035729fe43 |
work_keys_str_mv |
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