Limits...
MicroRNA-302/367 cluster governs hESC self-renewal by dually regulating cell cycle and apoptosis pathways.

Zhang Z, Hong Y, Xiang D, Zhu P, Wu E, Li W, Mosenson J, Wu WS - Stem Cell Reports (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

Show MeSH
A Model for Action of miR-302/367 Cluster in Regulation of Cell Cycle and Apoptosis in hESCsmiR-302/367 cluster is inducible by sodium butyrate in hESCs, and it is required to sustain expression of key cell cycle regulators such as BMI-1, CCND1, CCND2, and CDK6. At the same time, a minimum level of miR-302/367 cluster is needed to inhibit spontaneous apoptosis in hESCs by modulates expression of BCL-xL and BH3-only proapoptotic factor BNIP3L/Nix.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4400607&req=5

fig7: A Model for Action of miR-302/367 Cluster in Regulation of Cell Cycle and Apoptosis in hESCsmiR-302/367 cluster is inducible by sodium butyrate in hESCs, and it is required to sustain expression of key cell cycle regulators such as BMI-1, CCND1, CCND2, and CDK6. At the same time, a minimum level of miR-302/367 cluster is needed to inhibit spontaneous apoptosis in hESCs by modulates expression of BCL-xL and BH3-only proapoptotic factor BNIP3L/Nix.

Mentions: Butyrate is a histone deacetylase inhibitor and can promote ESC self-renewal across species, accumulate hESCs in S and G2/M phase, and delay the differentiation of hESCs (Ware et al., 2009). However, the molecular mechanisms underlying these actions of butyrate in hESCs remain elusive. We previously found that butyrate promotes cellular reprogramming by inducing the expression of miR-302/367 cluster (Zhang and Wu, 2013; Zhang et al., 2013). Here, we showed that butyrate could significantly induce expression of miR-302/367 cluster and downregulate its target gene BNIP3L/Nix in hESCs. Importantly, butyrate treatment rescues hESCs from apoptosis induced by knockdown of the endogenous miR-302/367 cluster. Thus, our data suggest that miR-302/367 cluster is a primary mediator for butyrate’s action in promoting hESC self-renewal and cell cycle progression (Figure 7).


MicroRNA-302/367 cluster governs hESC self-renewal by dually regulating cell cycle and apoptosis pathways.

Zhang Z, Hong Y, Xiang D, Zhu P, Wu E, Li W, Mosenson J, Wu WS - Stem Cell Reports (2015)

A Model for Action of miR-302/367 Cluster in Regulation of Cell Cycle and Apoptosis in hESCsmiR-302/367 cluster is inducible by sodium butyrate in hESCs, and it is required to sustain expression of key cell cycle regulators such as BMI-1, CCND1, CCND2, and CDK6. At the same time, a minimum level of miR-302/367 cluster is needed to inhibit spontaneous apoptosis in hESCs by modulates expression of BCL-xL and BH3-only proapoptotic factor BNIP3L/Nix.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400607&req=5

fig7: A Model for Action of miR-302/367 Cluster in Regulation of Cell Cycle and Apoptosis in hESCsmiR-302/367 cluster is inducible by sodium butyrate in hESCs, and it is required to sustain expression of key cell cycle regulators such as BMI-1, CCND1, CCND2, and CDK6. At the same time, a minimum level of miR-302/367 cluster is needed to inhibit spontaneous apoptosis in hESCs by modulates expression of BCL-xL and BH3-only proapoptotic factor BNIP3L/Nix.
Mentions: Butyrate is a histone deacetylase inhibitor and can promote ESC self-renewal across species, accumulate hESCs in S and G2/M phase, and delay the differentiation of hESCs (Ware et al., 2009). However, the molecular mechanisms underlying these actions of butyrate in hESCs remain elusive. We previously found that butyrate promotes cellular reprogramming by inducing the expression of miR-302/367 cluster (Zhang and Wu, 2013; Zhang et al., 2013). Here, we showed that butyrate could significantly induce expression of miR-302/367 cluster and downregulate its target gene BNIP3L/Nix in hESCs. Importantly, butyrate treatment rescues hESCs from apoptosis induced by knockdown of the endogenous miR-302/367 cluster. Thus, our data suggest that miR-302/367 cluster is a primary mediator for butyrate’s action in promoting hESC self-renewal and cell cycle progression (Figure 7).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

Show MeSH