Article

Cell Cycle Regulation by MicroRNAs in Embryonic Stem Cells

The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA 94143, USA.
Cancer Research (Impact Factor: 9.33). 06/2009; 69(10):4093-6. DOI: 10.1158/0008-5472.CAN-09-0309
Source: PubMed

ABSTRACT

The cell cycle is tightly orchestrated during normal development. Embryonic stem (ES) cells have a unique cell cycle structure, in which the G1/S restriction is largely absent, enabling cells to rapidly move through the G1 phase and enter the S phase. This hastened cell cycle allows the early embryo to rapidly grow. Recent experiments suggest that small noncoding RNAs, the microRNAs (miRNAs), play a central role in achieving this unique cell cycle structure. The responsible miRNAs function by suppressing multiple inhibitors of the G1/S transition. Expression of these miRNAs drops dramatically as the ES cells differentiate and as the G1 phase extends. Some of the same miRNAs are overexpressed in cancers, in which they can promote tumor growth, suggesting common mechanisms of miRNA-regulated cell cycle control in ES cells and cancers. This review discusses these recent findings in the context of broader knowledge of cell cycle control in normal and abnormal development.

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    • "One of the important functions of miRNAs is to regulate cell cycle progression and arrest by targeting the expression of multiple cell cycle regulatory genes. They can regulate cell proliferation by specifically targeting expression of cyclin-CDK complexes (involved in cellular proliferation) and CDK inhibitors (acting as growth suppressors) [Liu et al., 2008; Wang and Blelloch, 2009]. "
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    ABSTRACT: microRNA (miRNA) expression profiling of cancer versus normal cells may reveal the characteristic regulatory features that can be correlated to altered gene expression in both human and animal models of cancers. In this study, the comprehensive expression profiles of the 277 highly characterized miRNAs from the canine genome were evaluated in spontaneous canine mammary tumor (CMT) models harboring defects in a group of cell cycle regulatory and potent tumor suppressor genes of INK4/CDKN2 family including p16/INK4A, p14ARF, and p15/INK4B. A large number of differentially expressed miRNAs were identified in three CMT cell lines to potentially target oncogenes, tumor suppressor genes and cancer biomarkers. A group of the altered miRNAs were identified by miRNA target prediction tools for regulation of the INK4/CDKN2 family tumor suppressor genes. miRNA-141 was experimentally validated for INK4A 3'-UTR target binding in the CMT cell lines providing an essential mechanism for the post-transcriptional regulation of the INK4A tumor suppressor gene in CMT models. A well-recognized group of miRNAs including miR-21, miR-155, miR-9, miR-34a, miR-143/145, and miR-31 were found to be altered in both CMTs and human breast cancer. These altered miRNAs might serve as potential targets for advancing the development of future therapeutic reagents. These findings further strengthen the validity and use of canine breast cancers as appropriate models for the study of human breast cancers. J. Cell. Biochem. 116: 2956-2969, 2015. © 2015 Wiley Periodicals, Inc.
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    • "One of the important functions of miRNAs is to regulate cell cycle progression and arrest by targeting the expression of multiple cell cycle regulatory genes. They can regulate cell proliferation by specifically targeting expression of cyclin-CDK complexes (involved in cellular proliferation) and CDK inhibitors (acting as growth suppressors) [Liu et al., 2008; Wang and Blelloch, 2009]. "

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    • "One of the important functions of miRNAs is to regulate cell cycle progression and arrest by targeting the expression of multiple cell cycle regulatory genes. They can regulate cell proliferation by specifically targeting expression of cyclin-CDK complexes (involved in cellular proliferation) and CDK inhibitors (acting as growth suppressors) (Liu et al., 2008; Wang and Blelloch, 2009). This study identified groups of up-/down-regulated miRNAs and investigated their roles in promoting canine breast cancer and in targeting INK4 tumor suppressor and other cancer-associated genes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: microRNA (miRNA) expression profiling of cancer versus normal cells may reveal the characteristic regulatory features that can be correlated to altered gene expression in both human and animal models of cancers. In this study, the comprehensive expression profiles of the 277 highly characterized miRNAs from the canine genome were evaluated in spontaneous canine mammary tumor (CMT) models harboring defects in a group of cell cycle regulatory and potent tumor suppressor genes of INK4/CDKN2 family including p16/INK4A, p14ARF and p15/INK4B. A large number of differentially expressed miRNAs were identified in three CMT cell lines to potentially target oncogenes, tumor suppressor genes and cancer biomarkers. A group of the altered miRNAs were identified by miRNA target prediction tools for regulation of the INK4/CDKN2 family tumor suppressor genes. miRNA-141 was experimentally validated for INK4A 3'-UTR target binding in the CMT cell lines providing an essential mechanism for the post-transcriptional regulation of the INK4A tumor suppressor gene in CMT models. A well-recognized group of miRNAs including miR-21, miR-155, miR-9, miR-34a, miR-143/145, and miR-31 were found to be altered in both CMTs and human breast cancer. These altered miRNAs might serve as potential targets for advancing the development of future therapeutic reagents. These findings further strengthen the validity and use of canine breast cancers as appropriate models for the study of human breast cancers. [Full-text can be shared on request when there is relevant research interest]
    Full-text · Article · Jun 2015 · Journal of Cellular Biochemistry
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