miR-663 and the miRaculous Vascular Smooth Muscle Phenotypic Switch

Korff, Thomas; Pfisterer, Larissa; Schorpp-Kistner, Marina

doi:10.1161/circresaha.113.302578

Cited by 6 publications

(6 citation statements)

References 29 publications

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“…Cell proliferation/viability was controlled by WST-1 cell proliferation reagent (Roche Applied Science) as previously described [ 44 ]. Cell migration was investigated by wound healing assay as described before [ 44 , 45 ].…”

Section: Methodsmentioning

confidence: 99%

Elucidating mechanisms of sunitinib resistance in renal cancer: an integrated pathological-molecular analysis

et al. 2017

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Upon sunitinib treatment of metastatic renal cell carcinoma patients eventually acquire resistance. Our aim was to investigate microRNAs behind sunitinib resistance.We developed an in vivo xenograft and an in vitro model and compared morphological, immunhistochemical, transcriptomical and miRNome data changes during sunitinib response and resistance by performing next-generation mRNA and miRNA sequencing. Complex bioinformatics (pathway, BioFunction and network) analysis were performed. Results were validated by in vitro functional assays.Our morphological, immunhistochemical, transcriptomical and miRNome data all pointed out that during sunitinib resistance tumor cells changed to migratory phenotype. We identified the downregulated miR-1 and miR-663a targeting FRAS1 (Fraser Extracellular Matrix Complex Subunit 1) and MDGA1 (MAM Domain Containing Glycosylphosphatidylinositol Anchor 1) in resistant tumors. We proved firstly miR-1-FRAS1 and miR-663a-MDGA1 interactions. We found that MDGA1 knockdown decreased renal cancer cell migration and proliferation similarly to restoration of levels of miR-1 and miR-663.Our results support the central role of cell migration as an adaptive mechanism to secure tumor survival behind sunitinib resistance. MDGA1, FRAS1 or the targeting miRNAs can be potential adjuvant therapeutic targets, through inhibition of cancer cell migration, thus eliminating the development of resistance and metastasis.

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Section: Methodsmentioning

confidence: 99%

Elucidating mechanisms of sunitinib resistance in renal cancer: an integrated pathological-molecular analysis

et al. 2017

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“…Furthermore, miR-663 was upregulated in HUVECs exposed to proatherogenic oxidized phospholipids and was found to play a permissive role in the induction of VEGF and activation of ATF4 branch of unfolded protein response in ECs [102,103]. Interestingly, however, miR-663 regulates VSMC phenotypic switching by targeting the transcription factors JunB/Myosin Light chain 9 [104–106]. These results suggest that miR-663 has a context-dependent and cell type-specific role in the pathophysiological process, as overexpression of this human-specific microRNA using an adenoviral construct reduced neointimal formation in a mouse model of neointimal hyperplasia [107].…”

Section: Mirnas Upregulated By D-flow or Osmentioning

confidence: 99%

Role of flow-sensitive microRNAs and long noncoding RNAs in vascular dysfunction and atherosclerosis

Kumar

Williams

Sur

et al. 2019

Vascular Pharmacology

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Atherosclerosis is the primary underlying cause of myocardial infarction, ischemic stroke, and peripheral artery disease. The disease preferentially occurs in arterial regions exposed to disturbed blood flow, in part, by altering expression of flow-sensitive coding- and non-coding genes. In this review, we summarize the role of noncoding RNAs, [microRNAs (miRNAs) and long noncoding RNAs(lncRNAs)], as regulators of gene expression and outline their relationship to the pathogenesis of atherosclerosis. While miRNAs are small noncoding genes that post-transcriptionally regulate gene expression by targeting mRNA transcripts, the lncRNAs regulate gene expression by diverse mechanisms, which are still emerging and incompletely understood. We focused on multiple flow-sensitive miRNAs such as, miR-10a, −19a, −23b, −17~92, −21, −663, −92a, −143/145, −101, −126, −712, −205, and −155 that play a critical role in endothelial function and atherosclerosis by targeting inflammation, cell cycle, proliferation, migration, apoptosis, and nitric oxide signaling. Flow-dependent regulation of lncRNAs is just emerging, and their role in vascular dysfunction and atherosclerosis is unknown. Here, we discuss the flow-sensitive lncRNA STEEL along with other lncRNAs studied in the context of vascular pathophysiology and atherosclerosis such as MALAT1, MIAT1, ANRIL, MYOSLID, MEG3, SENCR, SMILR, LISPR1, and H19. Also discussed is the use of these noncoding RNAs as potential biomarkers and therapeutics to reduce and regress atherosclerosis.

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“…In contrast, with the contractile phenotype disappearing, some signature proteins involved in the regulation of contraction of the SMC decreased, including multiple tropomyosins (TPM1, TPM2, TPM3) and calponin (CNN1). , We observed that several isoforms of these proteins had a consistent decreasing trend (Figure and Tables S3 and S4). Myosin regulatory subunit (MYL9), a crucial element of the contractile apparatus, followed the same pattern, being down-regulated. Laminin (LAMC1), another adhesive glycoprotein and a component of the basement membrane, has been found to maintain the cells in a contractile phenotype and was shown to decrease in our MS-based proteomic analysis.…”

Section: Resultsmentioning

confidence: 89%

“…1,50 We observed that several isoforms of these proteins had a consistent decreasing trend (Figure 9 and Tables S3 and S4). Myosin regulatory subunit (MYL9), a crucial element of the contractile apparatus, 51 followed the same pattern, being down-regulated. Laminin (LAMC1), another adhesive glycoprotein and a component of the basement membrane, has been found to maintain the cells in a contractile phenotype 52 and was shown to decrease in our MS-based proteomic analysis.…”

Section: Resultsmentioning

confidence: 91%

Evaluation and Application of Dimethylated Amino Acids as Isobaric Tags for Quantitative Proteomics of the TGF-β/Smad3 Signaling Pathway

Shi

Greer

et al. 2016

J. Proteome Res.

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miR-663 and the miRaculous Vascular Smooth Muscle Phenotypic Switch

Cited by 6 publications

References 29 publications

Elucidating mechanisms of sunitinib resistance in renal cancer: an integrated pathological-molecular analysis

Elucidating mechanisms of sunitinib resistance in renal cancer: an integrated pathological-molecular analysis

Role of flow-sensitive microRNAs and long noncoding RNAs in vascular dysfunction and atherosclerosis

Evaluation and Application of Dimethylated Amino Acids as Isobaric Tags for Quantitative Proteomics of the TGF-β/Smad3 Signaling Pathway

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