MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein. Zhu, Y., Lu, Y., Zhang, Q., Liu, J., Li, T., Yang, J., Zeng, C., & Zhuang, S. Nucleic Acids Research, 40(10):4615–4625, May, 2012.
Paper doi abstract bibtex 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.
@article{zhu_microrna-26ab_2012,
title = {{MicroRNA}-26a/b and their host genes cooperate to inhibit the {G1}/{S} transition by activating the {pRb} protein},
volume = {40},
issn = {0305-1048},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378857/},
doi = {10.1093/nar/gkr1278},
abstract = {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.},
number = {10},
urldate = {2021-03-29},
journal = {Nucleic Acids Research},
author = {Zhu, Ying and Lu, Yang and Zhang, Qi and Liu, Jing-Jing and Li, Tuan-Jie and Yang, Jian-Rong and Zeng, Chunxian and Zhuang, Shi-Mei},
month = may,
year = {2012},
pmid = {22210897},
pmcid = {PMC3378857},
pages = {4615--4625},
}
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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.","number":"10","urldate":"2021-03-29","journal":"Nucleic Acids Research","author":[{"propositions":[],"lastnames":["Zhu"],"firstnames":["Ying"],"suffixes":[]},{"propositions":[],"lastnames":["Lu"],"firstnames":["Yang"],"suffixes":[]},{"propositions":[],"lastnames":["Zhang"],"firstnames":["Qi"],"suffixes":[]},{"propositions":[],"lastnames":["Liu"],"firstnames":["Jing-Jing"],"suffixes":[]},{"propositions":[],"lastnames":["Li"],"firstnames":["Tuan-Jie"],"suffixes":[]},{"propositions":[],"lastnames":["Yang"],"firstnames":["Jian-Rong"],"suffixes":[]},{"propositions":[],"lastnames":["Zeng"],"firstnames":["Chunxian"],"suffixes":[]},{"propositions":[],"lastnames":["Zhuang"],"firstnames":["Shi-Mei"],"suffixes":[]}],"month":"May","year":"2012","pmid":"22210897","pmcid":"PMC3378857","pages":"4615–4625","bibtex":"@article{zhu_microrna-26ab_2012,\n\ttitle = {{MicroRNA}-26a/b and their host genes cooperate to inhibit the {G1}/{S} transition by activating the {pRb} protein},\n\tvolume = {40},\n\tissn = {0305-1048},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378857/},\n\tdoi = {10.1093/nar/gkr1278},\n\tabstract = {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. 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