Dataset Information

MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1.

ABSTRACT: Atherosclerosis, a hyperlipidemia-induced chronic inflammatory process of the arterial wall, develops preferentially at sites where disturbed laminar flow compromises endothelial cell (EC) function. Here we show that endothelial miR-126-5p maintains a proliferative reserve in ECs through suppression of the Notch1 inhibitor delta-like 1 homolog (Dlk1) and thereby prevents atherosclerotic lesion formation. Endothelial recovery after denudation was impaired in Mir126(-/-) mice because lack of miR-126-5p, but not miR-126-3p, reduced EC proliferation by derepressing Dlk1. At nonpredilection sites, high miR-126-5p levels in endothelial cells confer a proliferative reserve that compensates for the antiproliferative effects of hyperlipidemia, such that atherosclerosis was exacerbated in Mir126(-/-) mice. In contrast, downregulation of miR-126-5p by disturbed flow abrogated EC proliferation at predilection sites in response to hyperlipidemic stress through upregulation of Dlk1 expression. Administration of miR-126-5p rescued EC proliferation at predilection sites and limited atherosclerosis, introducing a potential therapeutic approach.

SUBMITTER: Schober A

PROVIDER: S-EPMC4398028 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1.

Schober Andreas A Nazari-Jahantigh Maliheh M Wei Yuanyuan Y Bidzhekov Kiril K Gremse Felix F Grommes Jochen J Megens Remco T A RT Heyll Kathrin K Noels Heidi H Hristov Michael M Wang Shusheng S Kiessling Fabian F Olson Eric N EN Weber Christian C

Nature medicine 20140302 4

Atherosclerosis, a hyperlipidemia-induced chronic inflammatory process of the arterial wall, develops preferentially at sites where disturbed laminar flow compromises endothelial cell (EC) function. Here we show that endothelial miR-126-5p maintains a proliferative reserve in ECs through suppression of the Notch1 inhibitor delta-like 1 homolog (Dlk1) and thereby prevents atherosclerotic lesion formation. Endothelial recovery after denudation was impaired in Mir126(-/-) mice because lack of miR-1 ...[more]

PMID: 24584117

Similar Datasets

Project description:BackgroundLung adenocarcinoma (LUAD) is currently the leading cause of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) play key roles in tumor occurrence and development as crucial cancer regulators. The present study aimed to explore the molecular mechanism and regulatory network of Linc00511 in LUAD and to identify new potential therapeutic targets for LUAD.MethodsReal-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine the relative Linc00511 levels in LUAD tissues and cells. The proliferation, apoptosis, migration, and invasion abilities of LUAD cells were assessed by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, flow cytometry, and a Transwell assay. Changes in hsa_miR-126-5p, hsa_miR-218-5p, and COL1A1 expression were analyzed using western blotting and RT-qPCR. Targeted binding between miR-126-5p/miR-218-5p and Linc00511 or COL1A1 was verified with a luciferase reporter system and confirmed by an RNA pulldown assay. The participation of the PI3K/AKT signaling pathway was confirmed via western blotting. Xenograft animal experiments were performed to detect the impact of Linc00511 on LUAD tumor growth in vivo.ResultsIn the present work, we observed that Linc00511 was upregulated in LUAD tissues and cells. Loss/gain-of-function experiments indicated that knockdown of Linc00511 significantly inhibited LUAD cell proliferation, migration and invasion and promoted LUAD cell apoptosis, whereas overexpression of Linc00511 showed the opposite effects. In addition, we determined that Linc00511 promoted COL1A1-mediated cell proliferation and cell motility by sponging miR-126-5p and miR-218-5p. Moreover, Linc00511 activated the PI3K/AKT signaling pathway through upregulation of COL1A1. Finally, silencing of Linc00511 inhibited LUAD tumor growth in vivo.ConclusionsLinc00511 acts as a competing endogenous RNA to regulate COL1A1 by targeting miR-126-5p and miR-218-5p, thereby promoting the proliferation and invasion of LUAD cells.

Project description:Protein tyrosine phosphatase non-receptor type 9 (PTPN9), also named PTP-MEG2, is an important member of the protein tyrosine phosphatase family that is involved in variety of human diseases. However, the role of PTPN9 in esophageal squamous cell carcinoma (ESCC) remains to be established. The present evaluated the potential effect and underlying mechanism of action of PTPN9 in ESCC. Immunohistochemistry was performed to detect PTPN9 protein expression in 84 ESCC tumor specimens and 30 normal esophageal tissues. The association between positive expression of PTPN9 and clinicopathological features and prognosis was analyzed. The prognostic role of PTPN9 was further investigated using multivariate regression analysis. PTPN9-small interfering RNA and microRNA (miR-126)-mimics were transfected into Eca109 cells to construct PTPN9 silencing and an miR-126 ectopic expression cell model. Reverse transcription-quantitative polymerase chain reaction, western blot analysis, cell counting kit-8, Transwell assays and flow cytometry were used to investigate the role of PTPN9 in the process of ESCC progression and its potential downstream signaling pathway. Immunohistochemical analysis revealed that PTPN9 was upregulated in ESCC tumor specimens compared with normal esophageal tissues. The χ2 test indicated that positive expression of PTPN9 was correlated with tumor node metastasis stage, tumor classification and node classification. Patients with PTPN9 positive expression had shorter survival time, compared with those that were PTPN9 negative. Multivariate regression analysis with the Cox proportional hazards regression model revealed that PTPN9 expression was a prognostic factor of overall survival for patients with ESCC. Using RNA interference, the present study demonstrated that knockdown of PTPN9 significantly suppressed cell proliferation and invasion in Eca109. Additionally, it was hypothesized that miR-126, described as a tumor suppressor in ESCC, may act at least in part via its inhibition of PTPN9 at the post-transcriptional level. To the best of our knowledge, this is the first study to demonstrate that PTPN9 is overexpressed in ESCC and associated with poor survival, and may therefore be important in the pathogenesis of ESCC.

Dataset Information

MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1.

Publications

MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets