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MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein

The functional association between intronic miRNAs and their host genes is still largely unknown. We found that three gene loci, which produced miR-26a and miR-26b, were embedded within introns of genes coding for the proteins of carboxy-terminal domain RNA polymerase II polypeptide A small phosphat...

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Autores principales: Zhu, Ying, Lu, Yang, Zhang, Qi, Liu, Jing-Jing, Li, Tuan-Jie, Yang, Jian-Rong, Zeng, Chunxian, Zhuang, Shi-Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2012
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378857/
https://www.ncbi.nlm.nih.gov/pubmed/22210897
http://dx.doi.org/10.1093/nar/gkr1278
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author Zhu, Ying
Lu, Yang
Zhang, Qi
Liu, Jing-Jing
Li, Tuan-Jie
Yang, Jian-Rong
Zeng, Chunxian
Zhuang, Shi-Mei
author_facet Zhu, Ying
Lu, Yang
Zhang, Qi
Liu, Jing-Jing
Li, Tuan-Jie
Yang, Jian-Rong
Zeng, Chunxian
Zhuang, Shi-Mei
author_sort Zhu, Ying
collection PubMed
description The functional association between intronic miRNAs and their host genes is still largely unknown. We found that three gene loci, which produced miR-26a and miR-26b, were embedded within introns of genes coding for the proteins of carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase (CTDSP) family, including CTDSPL, CTDSP2 and CTDSP1. We conducted serum starvation-stimulation assays in primary fibroblasts and two-thirds partial-hepatectomies in mice, which revealed that miR-26a/b and CTDSP1/2/L were expressed concomitantly during the cell cycle process. Specifically, they were increased in quiescent cells and decreased during cell proliferation. Furthermore, both miR-26 and CTDSP family members were frequently downregulated in hepatocellular carcinoma (HCC) tissues. Gain- and loss-of-function studies showed that miR-26a/b and CTDSP1/2/L synergistically decreased the phosphorylated form of pRb (ppRb), and blocked G1/S-phase progression. Further investigation disclosed that miR-26a/b directly suppressed the expression of CDK6 and cyclin E1, which resulted in reduced phosphorylation of pRb. Moreover, c-Myc, which is often upregulated in cancer cells, diminished the expression of both miR-26 and CTDSP family members, enhanced the ppRb level and promoted the G1/S-phase transition. Our findings highlight the functional association of miR-26a/b and their host genes and provide new insight into the regulatory network of the G1/S-phase transition.
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spelling pubmed-33788572012-06-20 MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein Zhu, Ying Lu, Yang Zhang, Qi Liu, Jing-Jing Li, Tuan-Jie Yang, Jian-Rong Zeng, Chunxian Zhuang, Shi-Mei Nucleic Acids Res RNA The functional association between intronic miRNAs and their host genes is still largely unknown. We found that three gene loci, which produced miR-26a and miR-26b, were embedded within introns of genes coding for the proteins of carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase (CTDSP) family, including CTDSPL, CTDSP2 and CTDSP1. We conducted serum starvation-stimulation assays in primary fibroblasts and two-thirds partial-hepatectomies in mice, which revealed that miR-26a/b and CTDSP1/2/L were expressed concomitantly during the cell cycle process. Specifically, they were increased in quiescent cells and decreased during cell proliferation. Furthermore, both miR-26 and CTDSP family members were frequently downregulated in hepatocellular carcinoma (HCC) tissues. Gain- and loss-of-function studies showed that miR-26a/b and CTDSP1/2/L synergistically decreased the phosphorylated form of pRb (ppRb), and blocked G1/S-phase progression. Further investigation disclosed that miR-26a/b directly suppressed the expression of CDK6 and cyclin E1, which resulted in reduced phosphorylation of pRb. Moreover, c-Myc, which is often upregulated in cancer cells, diminished the expression of both miR-26 and CTDSP family members, enhanced the ppRb level and promoted the G1/S-phase transition. Our findings highlight the functional association of miR-26a/b and their host genes and provide new insight into the regulatory network of the G1/S-phase transition. Oxford University Press 2012-05 2011-12-31 /pmc/articles/PMC3378857/ /pubmed/22210897 http://dx.doi.org/10.1093/nar/gkr1278 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle RNA
Zhu, Ying
Lu, Yang
Zhang, Qi
Liu, Jing-Jing
Li, Tuan-Jie
Yang, Jian-Rong
Zeng, Chunxian
Zhuang, Shi-Mei
MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein
title MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein
title_full MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein
title_fullStr MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein
title_full_unstemmed MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein
title_short MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein
title_sort microrna-26a/b and their host genes cooperate to inhibit the g1/s transition by activating the prb protein
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378857/
https://www.ncbi.nlm.nih.gov/pubmed/22210897
http://dx.doi.org/10.1093/nar/gkr1278
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