title: MicroRNA-302/367 cluster governs hESC self-renewal by dually regulating cell cycle and apoptosis pathways.
abstract: miR-302/367 is the most abundant miRNA cluster in human embryonic stem cells (hESCs) and can promote somatic cell reprogramming. However, its role in hESCs remains poorly understood. Here, we studied functional roles of the endogenous miR-302/367 cluster in hESCs by employing specific TALE-based transcriptional repressors. We revealed that miR-302/367 cluster dually regulates hESC cell cycle and apoptosis in dose-dependent manner. Gene profiling and functional studies identified key targets of the miR-302/367 cluster in regulating hESC self-renewal and apoptosis. We demonstrate that in addition to its role in cell cycle regulation, miR-302/367 cluster conquers apoptosis by downregulating BNIP3L/Nix (a BH3-only proapoptotic factor) and upregulating BCL-xL expression. Furthermore, we show that butyrate, a natural compound, upregulates miR-302/367 cluster expression and alleviates hESCs from apoptosis induced by knockdown of miR-302/367 cluster. In summary, our findings provide new insights in molecular mechanisms of how miR-302/367 cluster regulates hESCs.
authors: Department of Medicine and Cancer Center, Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL 60612, USA; Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA; Berkeley Stem Cell Center, University of California at Berkeley, Berkeley, CA 94720, USA.
authors: Zhonghui
authors: Z
authors: Zhang
authors: Department of Medicine and Cancer Center, Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Yuanfan
authors: Y
authors: Hong
authors: Department of Medicine and Cancer Center, Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL 60612, USA; Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
authors: Di
authors: D
authors: Xiang
authors: Department of Medicine and Cancer Center, Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL 60612, USA; Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
authors: Pei
authors: P
authors: Zhu
authors: Department of Medicine and Cancer Center, Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Elise
authors: E
authors: Wu
authors: Department of Medicine and Cancer Center, Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Wen
authors: W
authors: Li
authors: Department of Medicine and Cancer Center, Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Jeffrey
authors: J
authors: Mosenson
authors: Department of Medicine and Cancer Center, Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL 60612, USA; Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA; Berkeley Stem Cell Center, University of California at Berkeley, Berkeley, CA 94720, USA. Electronic address: wuwenshu@uic.edu.
authors: Wen-Shu
authors: WS
authors: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002087:Butyrates / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D005810:Multigene Family; D011518:Proto-Oncogene Proteins / Q000235:genetics; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C116838:BNIP3L protein, human; D002087:Butyrates; C532169:MIRN302A microRNA, human; C568081:MIRN367 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins