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