Stem cell-derived exosomes prevent pyroptosis and repair ischemic muscle injury through a novel exosome/circHIPK3/ FOXO3a pathway

Yan, Bing; Zhang, Yu; Liang, Chun; Liu, Bin; Ding, Fengzhi; Wang, Yanli; Zhu, Bao Ting; Zhao, Ranzun; Yu, Xiyong; Li, Yangxin

doi:10.7150/thno.42259

Cited by 118 publications

(93 citation statements)

References 43 publications

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“…Circular RNAs (circRNAs) are produced by back splicing and play a crucial role in both physiological and pathological processes [7][8][9], particularly cancer [10,11]. Based on accumulating evidence, circRNAs function through the following mechanisms: regulating gene expression in cis at the transcriptional level [12], acting as a microRNA "sponge" and inhibiting its function [13], interacting with RNA binding proteins that regulate transcription [14], encoding peptides [15], and other functions.…”

mentioning

confidence: 99%

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia

Wang

Bian

et al. 2021

J Transl Med

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Background As a common haematological malignancy, acute myeloid leukaemia (AML), particularly with extramedullary infiltration (EMI), often results in a high mortality rate and poor prognosis. Circular RNAs (circRNAs) regulate biological and pathogenic processes, suggesting a potential role in AML. We have previously described the overall alterations in circRNAs and their regulatory networks between patients with AML presenting with and without EMI. This study aims to find new prognostic and therapeutic targets potentially associated with AML. Methods qRT-PCR was performed on samples from 40 patients with AML and 15 healthy controls. The possibility of using circPLXNB2 (circRNA derived from PLXNB2) as a diagnostic and prognostic biomarker for AML was analysed with multiple statistical methods. In vitro, the function of circPLXNB2 was studied by lentivirus transfection, CCK-8 assays, flow cytometry, and Transwell experiments. Western blotting and qRT-PCR were performed to detect the expression of related proteins and genes. The distribution of circPLXNB2 in cells was observed using RNA fluorescence in situ hybridization (RNA-FISH). We also investigated the role of circPLXNB2 by establishing AML xenograft models in NOD/SCID mice. Results By analysing the results of qRT-PCR detection of clinical samples, the expression of the circPLXNB2 and PLXNB2 mRNAs were significantly increased in patients with AML, more specifically in patients with AML presenting with EMI. High circPLXNB2 expression was associated with an obviously shorter overall survival and leukaemia-free survival of patients with AML. The circPLXNB2 expression was positively correlated with PLXNB2 mRNA expression, as evidenced by Pearson’s correlation analysis. RNA-FISH revealed that circPLXNB2 is mainly located in the nucleus. In vitro and in vivo, circPLXNB2 promoted cell proliferation and migration and inhibited apoptosis. Notably, circPLXNB2 also increased the expression of PLXNB2, BCL2 and cyclin D1, and reduced the expression of BAX. Conclusion In summary, we validated the high expression of circPLXNB2 and PLXNB2 in patients with AML. Elevated circPLXNB2 levels were associated with poor clinical outcomes in patients with AML. Importantly, circPLXNB2 accelerated tumour growth and progression, possibly by regulating PLXNB2 expression. Our study highlights the potential of circPLXNB2 as a new prognostic predictor and therapeutic target for AML in the future.

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confidence: 99%

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia

Wang

Bian

et al. 2021

J Transl Med

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“…Liu et al (2020c) found that cotransplantation of a chitosan thermosensitive hydrogel with BMSCs contributed to a better outcome in myocardial infarction, which is manifested by the inhibition of inflammatory response and alleviation of pyroptosis in vascular endothelial cells. There were also studies on MSC-derived miRNAs or circular RNAs (circRNAs) downregulating pyroptotic components in hypoxia/reoxygenation renal epithelial cells or ischemic muscle (Yuan et al, 2017;Yan et al, 2020). Besides, Kong and his group transplanted IL-37 gene-modified MSCs into rats model of intestinal ischemia-reperfusion injury and found that the expression of NLRP3 and downstream targets (cleaved caspase-1, IL-1β, and IL-18) were observably lessened (Kong et al, 2020).…”

Section: Mscs and Pyroptosis In Ischemic Strokementioning

confidence: 99%

Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke

Liu

Huang

et al. 2021

Front. Neurosci.

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Ischemic stroke is a leading cause of death worldwide; currently available treatment approaches for ischemic stroke are to restore blood flow, which reduce disability but are time limited. The interruption of blood flow in ischemic stroke contributes to intricate pathophysiological processes. Oxidative stress and inflammatory activity are two early events in the cascade of cerebral ischemic injury. These two factors are reciprocal causation and directly trigger the development of autophagy. Appropriate autophagy activity contributes to brain recovery by reducing oxidative stress and inflammatory activity, while autophagy dysfunction aggravates cerebral injury. Abundant evidence demonstrates the beneficial impact of mesenchymal stem cells (MSCs) and secretome on cerebral ischemic injury. MSCs reduce oxidative stress through suppressing reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation and transferring healthy mitochondria to damaged cells. Meanwhile, MSCs exert anti-inflammation properties by the production of cytokines and extracellular vesicles, inhibiting proinflammatory cytokines and inflammatory cells activation, suppressing pyroptosis, and alleviating blood–brain barrier leakage. Additionally, MSCs regulation of autophagy imbalances gives rise to neuroprotection against cerebral ischemic injury. Altogether, MSCs have been a promising candidate for the treatment of ischemic stroke due to their pleiotropic effect.

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“…Similarly, Xiang et al (2020) found that circ-Foxo3 was highly expressed in Gastric cancer cell lines and confirmed the existence of the circ-Foxo3/miR-143-3p/USP44 axis via a series of assays based on bioinformatics analysis Kong et al (2020) identified that circ-Foxo3, which targets SLC25A15, combined miR-29a-3p to promote the proliferation, invasion, apoptosis and tumorigenesis of prostate cancer. Besides, Yan et al (2020) demonstrated that circHIPK3, increasing Foxo3a expression, serves as a miR-421 sponge and inhibited inflammation to prevent ischemic injury.…”

Section: Functionsmentioning

confidence: 99%

Circular RNA Foxo3: A Promising Cancer-Associated Biomarker

Yang

Zhao

et al. 2021

Front. Genet.

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Circular RNAs (circRNAs) are a class of novel non-coding RNAs (ncRNAs). Emerging evidence demonstrates that circRNAs play crucial roles in many biological processes by regulating linear RNA transcription, downstream gene expression and protein or peptide translation. Meanwhile, recent studies have suggested that circRNAs have the potential to be oncogenic or anti-oncogenic and play vital regulatory roles in the initiation and progression of tumors. Circular RNA Forkhead box O3 (circ-Foxo3, hsa_circ_0006404) is encoded by the human FOXO3 gene and is one of the most studied circular RNAs acting as a sponge for potential microRNAs (miRNAs) (Du et al., 2016). Previous studies have reported that circ-Foxo3 is involved in the development and tumorigenesis of a variety of cancers (bladder, gastric, acute lymphocytic leukemia, glioma, etc.). In this review, we summarize the current studies concerning circ-Foxo3 deregulation and the correlative mechanism in various human cancers. We also point out the potential clinical applications of this circRNA as a biomarker for cancer diagnosis and prognosis.

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Stem cell-derived exosomes prevent pyroptosis and repair ischemic muscle injury through a novel exosome/circHIPK3/ FOXO3a pathway

Cited by 118 publications

References 43 publications

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia

Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke

Circular RNA Foxo3: A Promising Cancer-Associated Biomarker

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