Modulation of miRNAs in Pulmonary Hypertension

Gupta, Sudhiranjan; Li, Li

doi:10.1155/2015/169069

Cited by 28 publications

(27 citation statements)

References 114 publications

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“…Numerous studies have been performed on the role and related mechanism of miRNAs in numerous different kinds of diseases (9)(10)(11)(12). miRNAs bind primarily to the 3'-untranslated region (3'UTR) of their target messenger RNAs (mRNAs) to reduce their stability and decrease the expression of target mRNAs at the post-transcriptional level (13), which play important roles in various biological processes including cell growth, proliferation, differentiation and death (14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

et al. 2015

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Abstract. MicroRNAs (miRNAs) are well known as important regulators in various cancer development. In the present study, we focused on the expression and biological function of miR-1291 in esophageal squamous cell carcinoma (ESCC). Compared with adjacent non-tumorous tissue samples, qRT-PCR data showed significant downregulation of miR-1291 in 54 ESCC tissue samples (P<0.05), which was also significantly associated with lymph node metastases and clinical stage (P<0.05). Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometric apoptosis assays were performed to detect the effect of miR-1291 upregulation, and the results showed inhibition of the proliferation, invasion and promotion of apoptosis in EC9706 and EC-1 cells. Using bioinformatic analyses, we found that mucin 1 (MUC1) was a potential target for miR-1291. Luciferase assays were performed to reveal that miR-1291 inhibited MUC1 expression by targeting the seed region of MUC1 3'-untranslated region (3'UTR). We also found that the expression of MUC1 lacking in 3'UTR abrogated the anti-invasion and pro-apoptosis function of miR-1291. Our results demonstrated the importance of miR-1291 in targeting MUC1 for the regulation of esophagus cancer growth, invasion and apoptosis, and may be helpful for developing new targets for early diagnosis or new therapeutic targets for ESCC.

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Section: Introductionmentioning

confidence: 99%

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

et al. 2015

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“…It has been linked to PAH but did not show a significant difference between patients and control subjects [ 54 ]. Noteworthy, in the hypoxic mouse and monocrotaline rat pulmonary hypertensive models, miR-92a antagomirs reduced PA muscularization [ 10 ], which could partially explain its correlation to the reactive component of impedance in this study. However, directionality between the two rat pulmonary hypertensive models were conflicting.…”

Section: Discussionmentioning

confidence: 75%

“…For brevity, we will limit our discussion to those miRNA candidates most relevant to PAH pathophysiology. miR-21: This has long been recognized as a key gene regulator in the development and progression of cardiovascular disease [ 8 , 10 ]. When upregulated, it is associated with cardiac injury and inflammation, suppressing apoptosis and increasing proliferation in both smooth muscle cells (SMCs) and endothelial cells (ECs) [ 9 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…In recent decades, microRNAs (miRNA) have been recognized as important regulators of gene expression in certain cancers [ 7 ] and PAH [ 8 , 9 ]. miRNAs are small noncoding RNA molecules, consisting of 12–25 nucleotides that bind to the 3'UTR of target messenger RNAs resulting in mRNA degradation or translation repression [ 10 ]. In some cases, these molecules appear in the circulation and, based on expression, offer a unique opportunity for noninvasively assessing organ function [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Circulating miRNAs in Pediatric Pulmonary Hypertension Show Promise as Biomarkers of Vascular Function

Kheyfets

Sucharov

Truong

et al. 2017

Oxidative Medicine and Cellular Longevity

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Background/Objectives The objective of this study was to evaluate the utility of circulating miRNAs as biomarkers of vascular function in pediatric pulmonary hypertension. Method Fourteen pediatric pulmonary arterial hypertension patients underwent simultaneous right heart catheterization (RHC) and blood biochemical analysis. Univariate and stepwise multivariate linear regression was used to identify and correlate measures of reactive and resistive afterload with circulating miRNA levels. Furthermore, circulating miRNA candidates that classified patients according to a 20% decrease in resistive afterload in response to oxygen (O2) or inhaled nitric oxide (iNO) were identified using receiver-operating curves. Results Thirty-two circulating miRNAs correlated with the pulmonary vascular resistance index (PVRi), pulmonary arterial distensibility, and PVRi decrease in response to O2 and/or iNO. Multivariate models, combining the predictive capability of multiple promising miRNA candidates, revealed a good correlation with resistive (r = 0.97, P2−tailed < 0.0001) and reactive (r = 0.86, P2−tailed < 0.005) afterloads. Bland-Altman plots showed that 95% of the differences between multivariate models and RHC would fall within 0.13 (mmHg−min/L)m2 and 0.0085/mmHg for resistive and reactive afterloads, respectively. Circulating miR-663 proved to be a good classifier for vascular responsiveness to acute O2 and iNO challenges. Conclusion This study suggests that circulating miRNAs may be biomarkers to phenotype vascular function in pediatric PAH.

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“…14 In addition, these approaches might also correct the levels of multiple different microRNAs (microRNA 21, microRNA 17-92 cluster and microRNA 145), which could represent promising therapeutic approaches in hypoxic PAH. 19 Clinical observations by Camerini et al 20 revealed different results by using nifedipine in patients with primary PAH. With nifedipine (20 mg sublingually), a pronounced fall in pulmonary and systemic vascular resistances and a rise in cardiac output were obtained.…”

Section: Gene Mutations 21 Bmpr2mentioning

confidence: 99%

Pulmonary artery hypertension in childhood: The transforming growth factor-β superfamily-related genes

Yuan

2018

Pediatrics & Neonatology

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Pulmonary artery hypertension (PAH) is very rare in childhood, and it can be divided into heritable, idiopathic drug- and toxin-induced and other disease (connective tissue disease, human immunodeficiency virus infection, portal hypertension, congenital heart disease, or schistosomiasis)-associated types. PAH could not be interpreted solely by pathophysiological theories. The impact of the transforming growth factor-β superfamily-related genes on the development of PAH in children remains to be clarified. Pertinent literature on the transforming growth factor-β superfamily-related genes in relation to PAH in children published after the year 2000 was reviewed and analyzed. Bone morphogenetic protein receptor type II gene mutation promotes cell division or prevents cell death, resulting in an overgrowth of cells in small arteries throughout the lungs. About 20% of individuals with a bone morphogenetic protein receptor type II gene mutation develop symptomatic PAH. In heritable PAH, bone morphogenetic protein receptor type II mutations may be absent; while mutations of other genes, such as type I receptor activin receptor-like kinase 1 and the type III receptor endoglin (both associated with hereditary hemorrhagic telangiectasia), caveolin-1 and KCNK3, the gene encoding potassium channel subfamily K, member 3, can be detected, instead. Gene mutations, environmental changes and acquired adjustment, etc. may explain the development of PAH. The researches on PAH rat model and familial PAH members may facilitate the elucidations of the mechanisms and further provide theories for prophylaxis and treatment of PAH.

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Modulation of miRNAs in Pulmonary Hypertension

Cited by 28 publications

References 114 publications

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

Circulating miRNAs in Pediatric Pulmonary Hypertension Show Promise as Biomarkers of Vascular Function

Pulmonary artery hypertension in childhood: The transforming growth factor-β superfamily-related genes

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