MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines.
| Title: | MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. |
|---|---|
| Authors: | Baroukh N; INSERM, U145, Nice, F-06107, France.; Ravier MA; Loder MK; Hill EV; Bounacer A; Scharfmann R; Rutter GA; Van Obberghen E |
| Source: | The Journal of biological chemistry [J Biol Chem] 2007 Jul 06; Vol. 282 (27), pp. 19575-88. Date of Electronic Publication: 2007 Apr 26. |
| Publication Type: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology; Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| MeSH Terms: | Gene Expression Regulation, Developmental/*physiology ; Hepatocyte Nuclear Factor 3-beta/*biosynthesis ; Insulin-Secreting Cells/*metabolism ; MicroRNAs/*metabolism ; Organogenesis/*physiology ; Signal Transduction/*physiology; Calcium/metabolism ; Cell Differentiation/physiology ; Glucose/metabolism ; Growth Hormone/genetics ; Growth Hormone/metabolism ; Hepatocyte Nuclear Factor 3-beta/genetics ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Insulin/genetics ; Insulin/metabolism ; Insulin-Secreting Cells/cytology ; MicroRNAs/genetics ; Potassium Channels, Inwardly Rectifying/genetics ; Potassium Channels, Inwardly Rectifying/metabolism ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Animals ; Cell Line ; Female ; Humans ; Insulin Secretion ; Mice ; Pregnancy ; Transfection ; Kcnj11 Channel |
| Abstract: | MicroRNAs (miRNAs) are short non-coding RNAs that have been implicated in fine-tuning gene regulation, although the precise roles of many are still unknown. Pancreatic development is characterized by the complex sequential expression of a gamut of transcription factors. We have performed miRNA expression profiling at two key stages of mouse embryonic pancreas development, e14.5 and e18.5. miR-124a2 expression was strikingly increased at e18.5 compared with e14.5, suggesting a possible role in differentiated beta-cells. Among the potential miR-124a gene targets identified by biocomputation, Foxa2 is known to play a role in beta-cell differentiation. To evaluate the impact of miR-124a2 on gene expression, we overexpressed or down-regulated miR-124a2 in MIN6 beta-cells. As predicted, miR-124a2 regulated Foxa2 gene expression, and that of its downstream target, pancreatic duodenum homeobox-1 (Pdx-1). Foxa2 has been described as a master regulator of pancreatic development and also of genes involved in glucose metabolism and insulin secretion, including the ATP-sensitive K(+) (K(ATP)) channel subunits, Kir6.2 and Sur-1. Correspondingly, miR-124a2 overexpression decreased, and anti-miR-124a2 increased Kir6.2 and Sur-1 mRNA levels. Moreover, miR-124a2 modified basal and glucose- or KCl-stimulated intracellular free Ca(2+) concentrations in single MIN6 and INS-1 (832/13) beta-cells, without affecting the secretion of insulin or co-transfected human growth hormone, consistent with an altered sensitivity of the beta-cell exocytotic machinery to Ca(2+). In conclusion, whereas the precise role of microRNA-124a2 in pancreatic development remains to be deciphered, we identify it as a regulator of a key transcriptional protein network in beta-cells responsible for modulating intracellular signaling. |
| Substance Nomenclature: | SY7Q814VUP (Calcium); IY9XDZ35W2 (Glucose); 9002-72-6 (Growth Hormone); 135845-92-0 (Hepatocyte Nuclear Factor 3-beta); 0 (Homeodomain Proteins); 0 (Insulin); 0 (MicroRNAs); 0 (Potassium Channels, Inwardly Rectifying); 0 (Trans-Activators); 0 (Kcnj11 Channel); 0 (Foxa2 protein, mouse); 0 (pancreatic and duodenal homeobox 1 protein) |
| Entry Date(s): | Date Created: 20070428 Date Completed: 20070917 Latest Revision: 20260128 |
| Update Code: | 20260130 |
| DOI: | 10.1074/jbc.M611841200 |
| PMID: | 17462994 |
| Database: | MEDLINE |
Comparative Study; Journal Article; Research Support, Non-U.S. Gov't