miR-132 controls pancreatic beta cell proliferation and survival in mouse model through the Pten/Akt/Foxo3 signaling

Abstract

Pi3k -Phosphatidylinositol-4,5-bisphosphate 3-kinase; Ras -Rat sarcoma; Raf -rapidly accelerated fibrosarcoma; Mapk -mitogen-activated protein kinase; Sos1 -Son of sevenless homolog 1; Gnb1 -G Protein Subunit Beta 1; Nras -Neuroblastoma RAS viral oncogene homolog; Pik3r1 -Phosphoinositide-3-Kinase Regulatory Subunit 1; Gnb -G Protein Subunit Beta; Fgfr3 -fibroblast growth factor receptor 3; Creb -cAMP response element-binding protein peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/233098 doi: bioRxiv preprint first posted online Dec. 12, 2017; Mziaut et al, 2018 3 Abstract Aim and hypothesis: microRNAs (miRNAs) play an integral role in maintaining beta cell function and identity.Deciphering their targets and precise role, however, remains a challenge. In this study we aimed to identify miRNAs and their downstream targets involved in regeneration of islet beta cells following partial pancreatectomy in mice. Methods:RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in control of beta cell regeneration. Altered expression of selected miRNAs, including miR- peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/233098 doi: bioRxiv preprint first posted online Dec. 12, 2017; Mziaut et al, 2018 4 Based on previous knowledge of its function, we chose to focus our attention on miR-132. Downregulation of miR-132 Conclusions/Interpretations:Our study provides compelling evidence for upregulation of miR-132 being critical for regeneration of mouse islet beta cells in vivo through downregulation of its target Pten.Hence, the miR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass.Keywords miR-132; beta cell function; beta cell regeneration; apoptosis; Pten; Akt; Foxo3; pancreatectomy, diabetes.peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/233098 doi: bioRxiv preprint first posted online Dec. 12, 2017; Mziaut et al, 2018 5 Research in ContextWhat is already known?• Several miRNAs, including miR-132, are known to regulate beta cell function and mass in several mouse models of diabetes db/db, ob/ob and high fat-diet. What is the key question?• Which are the miRNAs implicated in control of beta cell regeneration upon partial pancreatectomy and how?What are the new findings?• miR-132 is critical to promote regeneration of mouse beta cells in vivo following partial pancreatectomy• In vitro studies in mouse MIN6 cells indicate that miR-132 fosters beta cell proliferation by down-regulating the expression of phosphatase Pten, thereby tilting the balance between anti-apoptotic ...

Shikonin inhibits migration and invasion of triple-negative breast cancer cells by suppressing epithelial-mesenchymal transition via miR-17-5p/PTEN/Akt pathway

“…We discovered that the activity of EMT was increased or decreased in PTEN knocked-down or over-expressed BC cells respectively. Akt is key member of the PI3K/AKT axis, which is a major signalling pathway antagonized by PTEN [36]. Akt activation via phosphorylation (P-Akt) controls metastasis in a diversity of tumors [37,38].The downregulation of PTEN in BC cells was in parallel with the upregulation of Akt and p-Akt (Ser473).…”