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MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis

MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of noncoding RNAs. Here, we focused on the function and molecular mechanism of miR-1 and its potential clinical application in clear cell renal cell carcinoma (ccRCC). First, miR-1 w...

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Autores principales: Xiao, Haibing, Zeng, Jin, Li, Heng, Chen, Ke, Yu, Gan, Hu, Junhui, Tang, Kun, Zhou, Hui, Huang, Qihong, Li, Anping, Li, Yi, Ye, Zhangqun, Wang, Ji, Xu, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537008/
https://www.ncbi.nlm.nih.gov/pubmed/26036633
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author Xiao, Haibing
Zeng, Jin
Li, Heng
Chen, Ke
Yu, Gan
Hu, Junhui
Tang, Kun
Zhou, Hui
Huang, Qihong
Li, Anping
Li, Yi
Ye, Zhangqun
Wang, Ji
Xu, Hua
author_facet Xiao, Haibing
Zeng, Jin
Li, Heng
Chen, Ke
Yu, Gan
Hu, Junhui
Tang, Kun
Zhou, Hui
Huang, Qihong
Li, Anping
Li, Yi
Ye, Zhangqun
Wang, Ji
Xu, Hua
author_sort Xiao, Haibing
collection PubMed
description MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of noncoding RNAs. Here, we focused on the function and molecular mechanism of miR-1 and its potential clinical application in clear cell renal cell carcinoma (ccRCC). First, miR-1 was significantly downregulated in 87.8% renal cancer samples compared with corresponding noncancerous tissues (NCT), which was significantly associated with clinical stage, T classification and poor overall survival. Functional study demonstrated that enforced overexpression of miR-1 in renal cancer cells inhibited proliferation and metastasis in vitro and in vivo. Conversely, miR-1 inhibitor silencing miR-1 expression promoted cell proliferation and metastasis in ccRCC. CDK4, CDK6, Caprin1 and Slug were each directly targeted for inhibition by miR-1 and restoring their expression reversed miR-1-mediated inhibition of cell cycle progression and metastasis. Taken together, our findings established a tumor suppressive role for miR-1 in the progression of ccRCC by targeting CDK4, CDK6, Caprin1 and Slug and suggested miR-1 can be served as a novel potential therapeutic target for ccRCC.
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spelling pubmed-45370082015-08-26 MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis Xiao, Haibing Zeng, Jin Li, Heng Chen, Ke Yu, Gan Hu, Junhui Tang, Kun Zhou, Hui Huang, Qihong Li, Anping Li, Yi Ye, Zhangqun Wang, Ji Xu, Hua Oncotarget Research Paper MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of noncoding RNAs. Here, we focused on the function and molecular mechanism of miR-1 and its potential clinical application in clear cell renal cell carcinoma (ccRCC). First, miR-1 was significantly downregulated in 87.8% renal cancer samples compared with corresponding noncancerous tissues (NCT), which was significantly associated with clinical stage, T classification and poor overall survival. Functional study demonstrated that enforced overexpression of miR-1 in renal cancer cells inhibited proliferation and metastasis in vitro and in vivo. Conversely, miR-1 inhibitor silencing miR-1 expression promoted cell proliferation and metastasis in ccRCC. CDK4, CDK6, Caprin1 and Slug were each directly targeted for inhibition by miR-1 and restoring their expression reversed miR-1-mediated inhibition of cell cycle progression and metastasis. Taken together, our findings established a tumor suppressive role for miR-1 in the progression of ccRCC by targeting CDK4, CDK6, Caprin1 and Slug and suggested miR-1 can be served as a novel potential therapeutic target for ccRCC. Impact Journals LLC 2015-04-23 /pmc/articles/PMC4537008/ /pubmed/26036633 Text en Copyright: © 2015 Xiao et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Xiao, Haibing
Zeng, Jin
Li, Heng
Chen, Ke
Yu, Gan
Hu, Junhui
Tang, Kun
Zhou, Hui
Huang, Qihong
Li, Anping
Li, Yi
Ye, Zhangqun
Wang, Ji
Xu, Hua
MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis
title MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis
title_full MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis
title_fullStr MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis
title_full_unstemmed MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis
title_short MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis
title_sort mir-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537008/
https://www.ncbi.nlm.nih.gov/pubmed/26036633
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