Hsa‐miR‐5582‐3P regulatory effect on TGFβ signaling through targeting of TGFβ‐R1, TGFβ‐R2, SMAD3, and SMAD4 transcripts

Bakhshmand, Elham Abedini; Soltani, Bahram Mohammad; Fasihi, Ali; Mowla, Seyed Javad

doi:10.1002/jcb.27314

Cited by 7 publications

(3 citation statements)

References 40 publications

(95 reference statements)

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“…Differential expression in disease states has been identified for miR-3182 [38, 39]. It has been reported that overexpression of miR-5582-3P affects TGFβ signaling through targeting [40] and that mirR-6863 is deregulated in FTO knockdown cells [41]. Assessment of the regulatory effects of miRNAs on targets relies on correct identification of miRNA-target interactions.…”

Section: Discussionmentioning

confidence: 99%

Three miRNAs cooperate with host genes involved in human cardiovascular disease

2019

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Background Understanding the roles of miRNAs in cardiovascular disease remains a challenge. Genomic linkage indicates a functional relationship between intronic miRNAs and their host genes. However, few studies have shown functional association between intronic miRNAs and their host coding genes that are genetically associated with cardiovascular disease. Methods In this study, we investigated functional relationship between three protein-coding genes genetically associated with cardiovascular disease, i.e., CDH13, SLC12A3, and CKAP5, and their intronic miRNAs using a data-driven approach. Results We found that the three protein-coding genes functionally interact with targets of their intronic miRNAs, i.e., miR-3182, miR-6863, and miR-5582, in a tissue-specific pattern. The intronic miRNAs preferentially impact important genes for the three host genes in the network, indicating their roles in maintaining the integrity of the interactome where the host genes are involved. Targets of the intronic miRNAs display functional similarity to the host genes. We furthermore present sets of target genes for future investigation on the possible miRNA-target interactions that potentially contribute to cardiovascular diseases. Conclusions Our work provides new insight into the regulatory network of the cardiovascular-associated pathways and opens the possibility for future experimental research. Electronic supplementary material The online version of this article (10.1186/s40246-019-0232-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Three miRNAs cooperate with host genes involved in human cardiovascular disease

2019

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“… hsa-miR-874 Decreased expression was associated with poor overall survival of ESCC patients, targets STAT3 [ 101 ]. hsa-miR-5585 Regulates cell cycle progression in human colorectal carcinoma cells, decreases expression of TGFβ-R1 , TGFβ-R2 , SMAD3 , and SMAD4 [ 102 ]. AAA—aortic abdominal aneurysm, AMI—acute myocardial infraction, CAD—coronary artery disease, EGFR—endothelial growth factor receptor, ESCC—esophagal squamous cells carcinoma, HCC—human colorectal cancer, HEY1—hairy/enhancer-of-split related with YRPW motif protein 1, HIF-1α—hypoxia induced factor 1α, HOXB1—homeobox B1, hUCMSCs—human umbilical cord mesenchymal stem cells, MALAT1—metastasis associated lung adenocarcinoma transcript 1, MAPK—mitogen activated protein kinase, mTOR—mammalian target of rapamycin, NF-κB—necrotic factor κB, NOTCH—translocation-associated protein, PI3K/AKT—phosphoinositide 3-kinases/protein kinase B, PTEN—phosphatase and tensin homolog deleted on chromosome ten, T2D—type 2 diabetes, TAA—thoracic aortic aneurysm, TGF-β—tumor growth factor β, TGFβ-R1—tumor growth factor β receptor 1, TGFβ-R2—tumor growth factor β receptor 2, SIRT7—sirtuin 7, SMAD3—decapentaplegic homolog 3, SMAD4—decapentaplegic homolog 4, STAT3—signal transducer and activator of transcription 3, SUFU—suppressor of fused homolog, Wnt—wingless-type MMTV integration site family of genes, VEGF—vascular endothelial growth factor, VEGFA—vascular endothelial growth factor A, VEGFR2—vascular endothelial growth factor receptor 2, VSMCs—vascular smooth muscle cells.…”

Section: Abdominal Aorta Aneurysm and Control Groups Constructionmentioning

confidence: 99%

Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm

Zalewski

Ruszel

Stępniewski

et al. 2020

JCM

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Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.

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“…Thus, elaborating the molecular regulators of this pathway helps in understanding the mechanisms that leads to diseases. TGFβ signaling pathway has been reported to be regulated by several known miRNAs [23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Downregulated miR-495-3p in colorectal cancer targets TGFβR1, TGFβR2, SMAD4 and BUB1 genes and induces cell cycle arrest

Soltani

Kabiri

Medlej

et al. 2019

Preprint

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• Background: Hsa-miR-495 (miR-495) has been extensively investigated in cancer initiation and progression. On the other hand, our bioinformatics analysis suggested that miR-495 exert its effects through targeting of TGFβ signaling components. • Methods & Results: In order to investigate such effect, miR-495 precursor was overexpressed in HEK293T and HCT116 cells, that it was followed by downregulation of TGFβR1, TGFβR2, SMAD4 and BUB1 putative target genes, detected by RT-qPCR. Also, luciferase assay supported direct interaction of miR-495 with 3’UTR sequences of TGFβR1, TGFβR2, SMAD4 and BUB1 genes. Furthermore, a negative correlation of expression between miR-495-3p and these target genes was deduced in a set of colorectal and breast cancer cell lines. Then, flow cytometry analysis showed that the overexpression of miR-495 in HCT116 and HEK293T resulted in an arrest at the G1 phase. Consistently, western blotting analysis showed a significant reduction of the Cyclin D1 protein in the cells overexpressing miR-495, pointing to downregulation of TGFβ signaling pathway and cell cycle arrest. Finally, microarray data analysis showed that miR-495-3p is significantly downregulated in colorectal tumors, compared to the normal pairs. • Conclusions: Overall, results of current study introduced miR-495-3p as a cell cycle progression suppressor, which negatively regulates TGFβR1, TGFβR2, SMAD4 and BUB1 genes. This finding suggests miR-495-3p as a tumor suppressor candidate for further evaluation.

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Hsa‐miR‐5582‐3P regulatory effect on TGFβ signaling through targeting of TGFβ‐R1, TGFβ‐R2, SMAD3, and SMAD4 transcripts

Cited by 7 publications

References 40 publications

Three miRNAs cooperate with host genes involved in human cardiovascular disease

Three miRNAs cooperate with host genes involved in human cardiovascular disease

Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm

Downregulated miR-495-3p in colorectal cancer targets TGFβR1, TGFβR2, SMAD4 and BUB1 genes and induces cell cycle arrest

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