Transcription Factors Targeted by miRNAs Regulating Smooth Muscle Cell Growth and Intimal Thickening after Vascular Injury

Khachigian, Levon M.

doi:10.3390/ijms20215445

Cited by 17 publications

(23 citation statements)

References 95 publications

(107 reference statements)

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“…The present paper demonstrated that RORα negatively regulated STAT-3 and further decreased the expression levels of the target molecules of STAT-3. The regulation of biological development involves the regulation of transcription factors, non-coding RNA, DNA modification and other multi-level regulation mechanisms, in which transcription factors and miRNAs are closely associated in the regulatory network (22). The expression levels of miRNAs are regulated by complex transcription factors, and the expression of transcription factors themselves are regulated by miRNAs (23).…”

Section: Discussionmentioning

confidence: 99%

Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway

Sui

Yang

2021

Exp Ther Med

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Endothelial cells sense changes in blood flow shear stress and affect the progression of atherosclerotic plaques. Pyroptosis is an inflammatory form of cell death and has been implicated in cardiovascular diseases. Melatonin and its nuclear receptor retinoid-related orphan receptor α (RORα) have protective effects on the development of atherosclerosis. To date, whether melatonin can prevent endothelial cell pyroptosis and dysfunction in pathological shear stress remains unclear. In the present study, human umbilical vein endothelial cells (ECs) were cultured under low shear stress conditions (5 dyne/cm 2 ) for 24 h and treated with or without melatonin (2 µmol/l). The binding sites of the microRNA (miR)-223 promoter and RORα were predicted using the JASPAR website. Expression of pyroptosis-related proteins, including cleaved N-terminal gasdermin D, caspase-1, intercellular adhesion molecule 1 (ICAM-1) and nitric oxide (NO) were assessed. The results indicated that low shear stress increased pyroptosis and ICAM-1 expression, whereas it decreased NO levels. Melatonin alleviated pyroptosis and ICAM-1 expression and increased the production of NO in ECs. Further assessment revealed that low-level shear stress decreased RORα protein and mRNA expression, whereas melatonin would bind to RORα and thereby promoted miR-223 transcription in ECs. The present study also identified signal transducer and activator of transcription 3 (STAT-3) as a potential target gene of miR-223-3p. When transfected with miR-223 inhibitor, ECs up-regulated the expression of pyroptosis-related proteins and ICAM-1, and down-regulated NO levels. By contrast, silencing STAT-3 expression diminished the protective effect of miR-223. These results indicated that melatonin prevented ECs from undergoing pyroptosis and alleviated dysfunction via the RORα/miR-223/STAT-3 signalling pathway. This information could aid in the development of novel therapeutic approaches and provide new insights into atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway

Sui

Yang

2021

Exp Ther Med

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“…26,27 Additionally, overexpression of KLF4 has been studied in multiple malignant tumors and has been found to regulate various biological functions, including cell proliferation, survival and metastasis. 11,28,29 We have indicated that KLF4 was a downstream target of miR-7-5p. It has been previously confirmed that miR-9 increased the cell apoptosis in ovarian cancer by directly targeting KLF4.…”

Section: Discussionmentioning

confidence: 99%

<p>Downregulation of miR-7-5p Inhibits the Tumorigenesis of Esophagus Cancer via Targeting KLF4</p>

Shi¹,

Song²,

Gao³

et al. 2020

OTT

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Background: Esophageal cancer (EC) is one of the aggressive gastrointestinal malignancies. It has been reported that microRNAs (miRNAs) play key roles during the tumorigenesis of EC. To identify novel potential targets for EC, differential expressed miRNAs (DEG) between EC and adjacent normal tissues were analyzed with bioinformatics tool. Methods: The differential expression of miRNAs between EC and adjacent normal tissues was analyzed. CCK-8 and Ki67 staining were used to detect the cell proliferation. Flow cytometry was performed to test the cell apoptosis. The correlation between miR-7-5p and KLF4 was detected by dual-luciferase report assay. Gene and protein expression in EC cells or in tissues were measured by qRT-PCR and Western blot, respectively. Cell migration and invasion were detected with transwell assay. Xenograft mice model was established to investigate the role of miR-7-5p in EC tumorigenesis in vivo. Results: MiR-7-5p was found to be negatively correlated with the survival rate of patient with EC. In addition, downregulation of miR-7-5p significantly inhibited the growth and invasion of EC cells. Meanwhile, miR-7-5p directly targeted KLF4 in EC cells. Moreover, downregulation of miR-7-5p inhibited the tumorigenesis of EC via inactivating MAPK signaling pathway in vivo. Conclusion: Downregulation of miR-7-5p notably suppressed the progression of EC via targeting KLF4. Thus, miR-7-5p might serve as a new target for the treatment of EC.

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“…MicroRNAs (miRNAs) are a type of small (20‒25 nucleotides) non-coding RNAs regulating PTMs. Evidence from several studies has implied that miRNAs are essential factors in the mechanisms of vascular remodeling ( Khachigian, 2019 ). miR-145 is a modulator of VSMC phenotype.…”

Section: Modulations Of Klf5 In Vascular Remodelingmentioning

confidence: 99%

Current knowledge of Krüppel-like factor 5 and vascular remodeling: providing insights for therapeutic strategies

Xie

Chen

Wang

et al. 2021

Journal of Molecular Cell Biology

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Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krϋppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.

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Transcription Factors Targeted by miRNAs Regulating Smooth Muscle Cell Growth and Intimal Thickening after Vascular Injury

Cited by 17 publications

References 95 publications

Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway

Melatonin attenuates low shear stress‑induced pyroptosis and endothelial cell dysfunction via the RORα/miR‑223/STAT‑3 signalling pathway

<p>Downregulation of miR-7-5p Inhibits the Tumorigenesis of Esophagus Cancer via Targeting KLF4</p>

Current knowledge of Krüppel-like factor 5 and vascular remodeling: providing insights for therapeutic strategies

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