Dataset Information

Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p.

ABSTRACT: Ischemic preconditioning (IPC) has protective effects against ischemia-perfusion injury of organs. In the present study, we investigated the associated mechanisms after performing remote IPC (rIPC) of lower limbs by clamping abdominal aorta in mice. Subsequent experiments showed decreased damage and paralysis of lower limbs following spinal cord injury (SCI). Concomitantly, plasma vascular endothelial growth factor (VEGF) levels were increased 24?h after rIPC compared with those in sham-operated animals. In subsequent microRNA analyses, thirteen microRNAs were downregulated in exosomes 24?h after rIPC. Further studies of femoral CD34-positive bone marrow (BM) cells confirmed downregulation of these seven microRNAs 24?h after rIPC compared with those in sham-operated controls. Subsequent algorithm-based database searches suggested that two of the seven microRNAs bind to the 3' UTR of VEGF mRNA, and following transfection into CD34-positive BM cells, anti-miR-762, and anti-miR-3072-5p inhibitors led to increased VEGF concentrations. The present data suggest that rIPC transiently increases plasma VEGF levels by downregulating miR-762 and miR-3072-5p in CD34-positive BM cells, leading to protection against organ ischemia.

SUBMITTER: Ueno K

PROVIDER: S-EPMC5131337 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p.

Ueno Koji K Samura Makoto M Nakamura Tamami T Tanaka Yuya Y Takeuchi Yuriko Y Kawamura Daichi D Takahashi Masaya M Hosoyama Tohru T Morikage Noriyasu N Hamano Kimikazu K

Scientific reports 20161201

Ischemic preconditioning (IPC) has protective effects against ischemia-perfusion injury of organs. In the present study, we investigated the associated mechanisms after performing remote IPC (rIPC) of lower limbs by clamping abdominal aorta in mice. Subsequent experiments showed decreased damage and paralysis of lower limbs following spinal cord injury (SCI). Concomitantly, plasma vascular endothelial growth factor (VEGF) levels were increased 24 h after rIPC compared with those in sham-operated ...[more]

PMID: 27905554

Similar Datasets

Project description:Abnormal expression of microRNA (miR) is associated with the occurrence and progression of various types of cancers, including papillary thyroid carcinoma (PTC). In the present study, the aim was to explore miR?486?5p expression and its role in PTC, as well as to investigate the biological function of its potential target genes. The expression levels of miR?486?5p and its clinicopathological significance were examined in 507 PTC and 59 normal thyroid samples via The Cancer Genome Atlas (TCGA). Subsequently, the results were validated using data from Gene Expression Omnibus (GEO) and ArrayExpress. Receiver operating characteristic and summary receiver operating characteristic curves were used to assess the ability of miR?486?5p in distinguishing PTC from normal tissue. Furthermore, potential miR?486?5p mRNA targets were identified using 12 prediction tools and enrichment analysis was performed on the encoding genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The expression levels of miR?486?5p were consistently downregulated in PTC compared with in normal tissue across datasets from TCGA, GEO (GSE40807, GSE62054 and GSE73182) and ArrayExpress (E?MTAB?736). The results also demonstrated that miR?486?5p expression was associated with cancer stage (P=0.003), pathologic lymph node (P=0.047), metastasis (P=0.042), neoplasm (P=0.012) and recurrence (P=0.016) in patients with PTC. In addition, low expression of miR?486?5p in patients with PTC was associated with a worse overall survival. A total of 80 miR?486?5p?related genes were observed from at least 9 of 12 prediction platforms, and these were involved in 'hsa05200: Pathways in cancer' and 'hsa05206: MicroRNAs in cancer'. Finally, three hub genes, CRK like proto?oncogene, phosphatase and tensin homolog and tropomyosin 3, were identified as important candidates in tumorigenesis and progression of PTC. In conclusion, it may be hypothesized that miR?486?5p contributes towards PTC onset and progression, and may act as a clinical target. However, in vitro and in vivo experiments are required to validate the findings of the present study.

Project description:Over the latest decade, the role of microRNAs (miRNAs/miRs) has received more attention. miRNAs are small non-coding RNAs that may serve a role as oncogenes or tumor suppressor genes. Certain miRNAs regulate the apoptosis pathway by influencing pro- or anti-apoptotic genes. We hypothesized that increases in the expression of B cell lymphoma 2 (BCL2) and BCL2-like 1 (BCL2L1) genes, which have been reported in various types of cancer tissues, may be due to the downregulation of certain miRNAs. The present study aimed to identify miRNAs that target BCL2 and BCL2L1 anti-apoptotic genes in prostate cancer (PCa) clinical tissue samples. Certain candidate miRNAs were selected bioinformatically and their expression in PCa samples was analyzed and compared with that in benign prostatic hyperplasia (BPH) tissue samples. The candidate miRNAs that targeted BCL2 and BCL2L1 genes were searched in online databases (miRWalk, microRNA.org, miRDB and TargetScan). A total of 12 miRNAs that target the 3'-untranslated region of the aforementioned genes and/or for which downregulation of their expression has previously been reported in cancer tissues. A total of 30 tumor tissue samples from patients with PCa and 30 samples tissues from patients with BPH were obtained and were subjected to reverse transcription-quantitative polymerase chain reaction for expression analysis of 12 candidate miRNAs, and the BCL2 and BCL2L1 genes. Additionally, expression of 3 finally selected miRNAs and genes was evaluated in prostate cancer PC3 and DU145 cell lines and human umbilical vein endothelial cells. Among 12 miRNA candidates, the expression of miR-1266, miR-185 and miR-30c-2 was markedly downregulated in PCa tumor tissues and cell lines. Furthermore, downregulation of these miRNAs was associated with upregulation of the BCL2 and BCL2L1 genes. An inverse association between three miRNAs (miR-1266, miR-185 and miR-30c-2) and two anti-apoptotic genes (BCL2 and BCL2L1) may be considered for interventional miRNA therapy of PCa.

Dataset Information

Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p.

Publications

Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets