Exosomal Transfer of miR-185 Is Controlled by hnRNPA2B1 and Impairs Re-endothelialization After Vascular Injury

Si, Yi; Liu, Fei; Wang, Dongqing; Fang, Chao; Tang, X.; Guo, Baolei; Shi, Zhenyu; Dong, Zhihui; Guo, Daqiao; Yue, Jianing; Fu, Weiguo

doi:10.3389/fcell.2021.619444

Cited by 14 publications

(8 citation statements)

References 45 publications

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“…Our study shows that PABPC1 can increase expression of miR-21-5p, in ESCC cells, which is then encapsulated in ESCC cell-derived exosomes to target vessel endothelial cells and induce angiogenesis. Importantly, we further investigated how miR-21-5p is packaged into exosomes, showing that PABPC1 can bind miR-21-5p, through an ACUGAUG sequence, to direct miR-21-5p packaging into exosomes, similar to other studies showing involvement of other RBPs, such as hnRNPQ and hnRNPA2B1, in exosomal miRNA export [ 32 , 33 ]. Previous studies showed the pro-angiogenic properties of endogenous miR-21-5p and cancer cell derived-miR-21-5p to be dependent on KRIT1 and Spry1 in vessel endothelial cells [ 34 – 36 ].…”

Section: Discussionsupporting

confidence: 62%

PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p

Zhang

Chen

Liu

et al. 2022

J Exp Clin Cancer Res

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Background Emerging evidence has demonstrated that RNA-binding protein dysregulation is involved in esophageal squamous cell carcinoma (ESCC) progression. However, the role of poly (A) binding protein cytoplasmic 1 (PABPC1) in ESCC is unclear. We therefore aimed to explore the functions and potential mechanisms of PABPC1 in ESCC progression. Methods PABPC1 expression was characterized using immunohistochemistry and qRT-PCR in ESCC tissues and cell lines. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to detect histone acetylation in the promoter region of PABPC1. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of PABPC1 in ESCC angiogenesis and malignant procession. Results PABPC1 expression was upregulated in ESCC tissues compared with in normal esophageal epithelial tissues. Elevated PABPC1 expression was correlated with tumor cell differentiation and poor prognosis in patients. Sp1 and p300 cooperated to increase the level of H2K37ac in the PABPC1 promoter. Functionally, PABPC1 overexpression enhanced esophageal squamous cell proliferation and invasion by activating the IFN/IFI27 signaling pathway. PABPC1 interacted with eIF4G to increase the stability of IFI27 mRNA by competing with RNA exosomes in ESCC. Furthermore, PABPC1/IFI27 could increase miR-21-5p expression to enable exosomal delivery of miR-21-5p to human umbilical vein endothelial cells to increase angiogenesis via inhibiting CXCL10. Conclusion PABPC1 plays a critical role in ESCC malignant progression by interacting with eIF4G to regulate IFI27 mRNA stability and promote angiogenesis via exosomal miR-21-5p/CXCL10. Taken together, our results suggest that PABPC1 is a promising therapeutic target for ESCC.

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Section: Discussionsupporting

confidence: 62%

PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p

Zhang

Chen

Liu

et al. 2022

J Exp Clin Cancer Res

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“…1 E, F). As described in recent research, lysoPC induces the pyroptosis of human endothelial cells by activating the NLRP3 inflammasome, which is closely related to endothelial cell dysfunction [ 23 , 27 ]. Then, the impact of GDF11 on the expression of NLRP3, Casp1 p20, IL-1β, and GSDMD-N at the protein level was further investigated.…”

Section: Resultsmentioning

confidence: 99%

GDF11 alleviates neointimal hyperplasia in a rat model of artery injury by regulating endothelial NLRP3 inflammasome activation and rapid re-endothelialization

Gao

Liu

et al. 2022

J Transl Med

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Background Neointimal hyperplasia induced by interventional surgery can lead to progressive obliteration of the vascular lumen, which has become a major factor affecting prognosis. The rate of re-endothelialization is known to be inversely related to neointima formation. Growth differentiation factor 11 (GDF11) is a secreted protein with anti-inflammatory, antioxidant, and antiaging properties. Recent reports have indicated that GDF11 can improve vascular remodeling by maintaining the differentiated phenotypes of vascular smooth muscle cells. However, it is not known whether and how GDF11 promotes re-endothelialization in vascular injury. The present study was performed to clarify the influence of GDF11 on re-endothelialization after vascular injury. Methods An adult Sprague–Dawley rat model of common carotid artery balloon dilatation injury was surgically established. A recombinant adenovirus carrying GDF11 was delivered into the common carotid artery to overexpress GDF11. Vascular re-endothelialization and neointima formation were assessed in harvested carotid arteries through histomolecular analysis. CCK-8 analysis, LDH release and Western blotting were performed to investigate the effects of GDF11 on endothelial NLRP3 inflammasome activation and relevant signaling pathways in vitro. Results GDF11 significantly enhanced re-endothelialization and reduced neointima formation in rats with balloon-dilatation injury by suppressing the activation of the NLRP3 inflammasome. Administration of an endoplasmic reticulum stress (ER stress) inhibitor, 4PBA, attenuated endothelial NLRP3 inflammasome activation induced by lysophosphatidylcholine. In addition, upregulation of LOX-1 expression involved elevated ER stress and could result in endothelial NLRP3 inflammasome activation. Moreover, GDF11 significantly inhibited NLRP3 inflammasome-mediated endothelial cell pyroptosis by negatively regulating LOX-1-dependent ER stress. Conclusions We conclude that GDF11 improves re-endothelialization and can attenuate vascular remodeling by reducing endothelial NLRP3 inflammasome activation. These findings shed light on new treatment strategies to promote re-endothelialization based on GDF11 as a future target.

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“…Vascular permeability associated with the endothelial barrier function in the aorta was determined by the procedure using Evans Blue dye 57 . One hundred μL of 1% Evans Blue dye (Nacalai Tesque) dissolved in saline was intravenously injected into mice.…”

Section: Methodsmentioning

confidence: 99%

Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity

et al. 2022

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Whether a small GTPase RhoA plays a role in the pathology of abdominal aortic aneurysm (AAA) has not been determined. We show here that RhoA expression is reduced in human AAA lesions, compared with normal areas. Furthermore, incidence of AAA formation is increased in vascular smooth muscle cell (VSMC)-specific RhoA conditional knockout (cKO) mice. The contractility of the aortic rings and VSMCs from RhoA cKO mice is reduced, and expression of genes related to the VSMC contractility is attenuated by loss of RhoA. RhoA depletion activates the mitogen-activated protein (MAP) kinase signaling, including MAP4K4, in the aorta and VSMCs. Inhibition of MAP4K4 activity by DMX-5804 decreases AAA formation. Set, a binding protein to active RhoA, functions as an activator of MAP4K4 by sequestering PP2A, an inhibitor of MAP4K4, in the absence of RhoA. In conclusion, RhoA counteracts AAA formation through inhibition of MAP4K4 in cooperation with Set.

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Exosomal Transfer of miR-185 Is Controlled by hnRNPA2B1 and Impairs Re-endothelialization After Vascular Injury

Cited by 14 publications

References 45 publications

PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p

PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p

GDF11 alleviates neointimal hyperplasia in a rat model of artery injury by regulating endothelial NLRP3 inflammasome activation and rapid re-endothelialization

Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity

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