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MiR?29 promotes the proliferation of cultured rat neural stem/progenitor cells via the PTEN/AKT signaling pathway.

ABSTRACT: Neural stem/progenitor cells (NSPCs) are self?renewing, multipotent cells and remain in the human brain throughout an individual's lifetime. NSPCs are activated by brain damage and contribute towards repair and motor function recovery in the central nervous system (CNS). It was previously reported that miR?29 was involved in regulating proliferation, differentiation and survival in hepatocellular carcinoma, and osteoblast and mantle cell lymphoma; however, the effects of miR?29 on NSPCs remain unclear. In the present study, it was demonstrated via Cell Counting Kit?8 assays that overexpression of miR?29 promoted the viability of NPSCs, and downregulated the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) protein. Additionally, treatment with a PTEN?specific inhibitor (VO?OHpic trihydrate) abolished the effects of the miR?29 inhibitor on PTEN expression, as determined via western blotting. Flow cytometry and 5?bromo?2?deoxyuridine (BrdU) staining revealed that overexpression of miR?29 further promoted the proliferation of NSPCs; however, knocking down miR?29 inhibited cell proliferation. VO?OHpic trihydrate reversed the effects of miR?29 knockdown on cell proliferation. Furthermore, it was observed that overexpression of miR?29 increased the phosphorylation levels of AKT. Collectively, the results indicated that overexpression of miR?29 promoted the proliferation of cultured rat NSPCs and decreased the expression of PTEN protein, and that the activation of Akt may be a potential underlying mechanism. The present findings may provide novel insight for the development of strategies for stem cell?mediated treatment of CNS diseases.

SUBMITTER: Gao Y

PROVIDER: S-EPMC6691275 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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miR‑29 promotes the proliferation of cultured rat neural stem/progenitor cells via the PTEN/AKT signaling pathway.

Gao Yunan Y Qiao Hu H Lu Zhen Z Hou Yuxia Y

Molecular medicine reports 20190701 3

Neural stem/progenitor cells (NSPCs) are self‑renewing, multipotent cells and remain in the human brain throughout an individual's lifetime. NSPCs are activated by brain damage and contribute towards repair and motor function recovery in the central nervous system (CNS). It was previously reported that miR‑29 was involved in regulating proliferation, differentiation and survival in hepatocellular carcinoma, and osteoblast and mantle cell lymphoma; however, the effects of miR‑29 on NSPCs remain u ...[more]

PMID: 31257508

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Project description:ObjectiveMicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice.MethodsRNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including miR-132, was verified by RT-PCR. Potential targets of miR-132 were selected through bioinformatic data mining. Predicted miR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon miR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of miR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized miR-132-/- and control mice.ResultsPartial pancreatectomy significantly increased the number of BrdU+/insulin+ islet cells. Microarray profiling revealed that 14 miRNAs, including miR-132 and -141, were significantly upregulated in the LCM islets of the partially pancreatectomized mice compared to the LCM islets of the control mice. In the same comparison, miR-760 was the only downregulated miRNA. The changed expression of these miRNAs in the islets of the partially pancreatectomized mice was confirmed by RT-PCR only in the case of miR-132 and -141. Based on previous knowledge of its function, we focused our attention on miR-132. Downregulation of miR-132 reduced the proliferation of MIN6 cells while enhancing the levels of pro-apoptotic cleaved caspase-9. The opposite was observed in miR-132 overexpressing MIN6 cells. Microarray profiling, RT-PCR, and immunoblotting of the latter cells demonstrated their downregulated expression of Pten with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb and inactivation of pro-apoptotic Foxo3a via its phosphorylation. Downregulation of Pten was further confirmed in the LCM islets of pancreatectomized mice compared to the sham-operated mice. Moreover, overexpression of miR-132 correlated with increased proliferation of EndoC-βH1 cells. The regeneration of beta cells following partial pancreatectomy was lower in the miR-132/212-/- mice than the control littermates.ConclusionsThis study provides compelling evidence about the critical role of miR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the miR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass.

Dataset Information

MiR?29 promotes the proliferation of cultured rat neural stem/progenitor cells via the PTEN/AKT signaling pathway.

Publications

miR‑29 promotes the proliferation of cultured rat neural stem/progenitor cells via the PTEN/AKT signaling pathway.

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