Long noncoding RNAs C2dat1 enhances vascular smooth muscle cell proliferation and migration by targeting MiR‐34a‐5p

Wang, Hairong; Jin, Zhili; Tu, Pei Chi; Song, Wenhao; Gong, Yao; Chen, Deliang; Zhang, Lin; Zhang, Meichun; Gang-chen, Zhang

doi:10.1002/jcb.27070

Cited by 29 publications

(25 citation statements)

References 34 publications

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“…9 Another study reported that lncRNA-C2dat1 enhances VSMC proliferation and migration by targeting miR-34a-5p. 11 In previous work, we demonstrated that calcification/senescence of VSMCs is regulated by the lncRNA-ES3/miR-34c-5p/BMF axis. 12 However, that study did not elucidate the specific role of lncRNA-ES3 in calcification/senescence of VSMCs, and the overall mechanism remained largely uncharacterized.…”

Section: Introductionmentioning

confidence: 93%

LncRNA‐ES3 inhibition by Bhlhe40 is involved in high glucose–induced calcification/senescence of vascular smooth muscle cells

Zhong

Cui

Zhan

et al. 2020

Annals of the New York Academy of Sciences

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Long noncoding RNAs (lncRNAs) have been investigated as novel regulatory molecules involved in diverse biological processes. Our previous study demonstrated that lncRNA‐ES3 is associated with the high glucose–induced calcification/senescence of human aortic vascular smooth muscle cells (HA‐VSMCs). However, the mechanism of lncRNA‐ES3 in vascular calcification/aging remained largely unknown. Here, we report that the expression of basic helix‐loop‐helix family member e40 (Bhlhe40) was decreased significantly in HA‐VSMCs treated with high glucose, whereas the expression of basic leucine zipper transcription factor (BATF) was increased. Overexpression of Bhlhe40 and inhibition of BATF alleviated calcification/senescence of HA‐VSMCs, as confirmed by Alizarin Red S staining and the presence of senescence‐associated β‐galactosidase–positive cells. Moreover, we identified that Bhlhe40 regulates lncRNA‐ES3 in HA‐VSMCs by binding to the promoter region of the lncRNA‐ES3 gene (LINC00458). Upregulation or inhibition of lncRNA‐ES3 expression significantly promoted or reduced calcification/senescence of HA‐VSMCs, respectively. Additionally, we identified that lncRNA‐ES3 functions in this process by suppressing the expression of miR‐95‐5p, miR‐6776‐5p, miR‐3620‐5p, and miR‐4747‐5p. The results demonstrate that lncRNA‐ES3 triggers gene silencing of multiple miRNAs by binding to Bhlhe40, leading to calcification/senescence of VSMCs. Our findings suggest that pharmacological interventions targeting lncRNA‐ES3 may be therapeutically beneficial in ameliorating vascular calcification/aging.

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Section: Introductionmentioning

confidence: 93%

LncRNA‐ES3 inhibition by Bhlhe40 is involved in high glucose–induced calcification/senescence of vascular smooth muscle cells

Zhong

Cui

Zhan

et al. 2020

Annals of the New York Academy of Sciences

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“…14,15 In addition, SIRT1 plays an important protective role in the cardiovascular system through its functions on STAT3 deacetylation. [10][11][12][13][14][15] A study revealed that atherosclerosis in SIRT1 +/-Apo E −/− mice is decreased significantly compared with ApoE −/− counterparts. 10 SIRT1 can also suppress AngII-induced VSMCs proliferation and migration as well as phenotypic transformation, counteracting hypertensive angiopathy.…”

Section: Discussionmentioning

confidence: 99%

“…SIRT1 is an important inhibitory factor of AngII-induced VSMCs phenotypic transformation as well as proliferation and migration, acting by decreasing STAT3 acetylation and phosphorylation. [10][11][12][13][14][15] Therefore, we further explored whether WWP2 promotes STAT3 acetylation and phosphorylation by inhibiting the effect of SIRT1 on STAT3. As expected, co-immunoprecipitation assays results showed that WWP2 overexpression decreased the interaction between SIRT1 and STAT3 ( Figure 2E), whereas WWP2 knockdown increased the interaction between SIRT1 and STAT3 ( Figure 2F).…”

Section: Wwp2 Forms a Complex With Sirt1-stat3 Competing For The Imentioning

confidence: 99%

WWP2 regulates SIRT1‐STAT3 acetylation and phosphorylation involved in hypertensive angiopathy

Zhang

You

Tian

et al. 2020

J Cellular Molecular Medi

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WWP2 is a HECT‐type E3 ubiquitin ligase that regulates various physiological and pathological activities by binding to different substrates, but its function and regulatory mechanism in vascular smooth muscle cells (VSMCs) are still unknown. Here, we clarified the role of WWP2 in the regulation of SIRT1‐STAT3 and the impact of this regulatory process in VSMCs. We demonstrated that WWP2 expression was significantly increased in angiotensin II‐induced VSMCs model. Knockdown of WWP2 significantly inhibited angiotensin II‐induced VSMCs proliferation, migration and phenotypic transformation, whereas overexpression of WWP2 had opposite effects. In vivo experiments showed that vascular smooth muscle‐specific WWP2 knockout mice significantly relieved angiotensin II‐induced hypertensive angiopathy. Mechanistically, mass spectrometry and co‐immunoprecipitation assays identified that WWP2 is a novel interacting protein of SIRT1 and STAT3. Moreover, WWP2 formed a complex with SIRT1‐STAT3, inhibiting the interaction between SIRT1 and STAT3, then reducing the inhibitory effect of SIRT1 on STAT3, ensuing promoting STAT3‐K685 acetylation and STAT3‐Y705 phosphorylation in angiotensin II‐induced VSMCs and mice. In conclusion, WWP2 modulates hypertensive angiopathy by regulating SIRT1‐STAT3 and WWP2 suppression in VSMCs can alleviate hypertensive angiopathy vitro and vivo. These findings provide new insights into the treatment of hypertensive vascular diseases.

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“…LncRNA C2dat1 is a CaMK2D-associated transcript 1. LncRNA shows higher expression in CAD ( 90 ). C2dat1 binds to miR-34a and modulates its expression in CAD.…”

Section: Noncoding Rnas That Sponge Mirnas Involved In Aging and Regementioning

confidence: 99%

“…C2dat1 binds to miR-34a and modulates its expression in CAD. Overexpression of C2dat1 suppresses miR-34a expression and upregulates its target protein SIRT1, increasing VSMC growth and migration in CAD ( 91 ).…”

Section: Noncoding Rnas That Sponge Mirnas Involved In Aging and Regementioning

confidence: 99%

Molecular therapies delaying cardiovascular aging: disease- or health-oriented approaches

et al. 2020

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Regenerative medicine is a new therapeutic modality that aims to mend tissue damage by encouraging the reconstitution of physiological integrity. It represents an advancement over conventional therapies that allow reducing the damage but result in disease chronicization. Age-related decline in spontaneous capacity of repair, especially in organs like the heart that have very limited proliferative capacity, contributes in reducing the benefit of conventional therapy. ncRNAs are emerging as key epigenetic regulators of cardiovascular regeneration. Inhibition or replacement of miRNAs may offer reparative solutions to cardiovascular disease. The first part of this review article is devoted to illustrating novel therapies emerging from research on miRNAs. In the second part, we develop new therapeutic concepts emerging from genetics of longevity. Prolonged survival, as in supercentenarians, denotes an exceptional capacity to repair and cope with risk factors and diseases. These characteristics are shared with offspring, suggesting that the regenerative phenotype is heritable. New evidence indicates that genetic traits responsible for prolongation of health span in humans can be passed to and benefit the outcomes of animal models of cardiovascular disease. Genetic studies have also focused on determinants of accelerated senescence and related druggable targets. Evolutionary genetics assessing the genetic basis of adaptation and comparing successful and unsuccessful genetic changes in response to selection within populations represent a powerful basis to develop novel therapies aiming to prolong cardiovascular and whole organism health.

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Long noncoding RNAs C2dat1 enhances vascular smooth muscle cell proliferation and migration by targeting MiR‐34a‐5p

Cited by 29 publications

References 34 publications

LncRNA‐ES3 inhibition by Bhlhe40 is involved in high glucose–induced calcification/senescence of vascular smooth muscle cells

LncRNA‐ES3 inhibition by Bhlhe40 is involved in high glucose–induced calcification/senescence of vascular smooth muscle cells

WWP2 regulates SIRT1‐STAT3 acetylation and phosphorylation involved in hypertensive angiopathy

Molecular therapies delaying cardiovascular aging: disease- or health-oriented approaches

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