Contents of exosomes derived from adipose tissue and their regulation on inflammation, tumors, and diabetes DOI Creative Commons
Yanwen Wang, Qingfeng Li, Shuang‐Bai Zhou

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 16, 2024

Adipose tissue (AT) serves as an energy-capacitive organ and performs functions involving paracrine- endocrine-mediated regulation via extracellular vesicles (EVs) secretion. Exosomes, a subtype of EVs, contain various bioactive molecules with regulatory effects, such nucleic acids, proteins, lipids. AT-derived exosomes (AT-exos) include derived from cells in AT, including adipocytes, adipose-derived stem (ADSCs), macrophages, endothelial cells. This review aimed to comprehensively evaluate the impacts different AT-exos on physiological pathological processes. The contents adipocyte-derived ADSC-derived are compared simultaneously, highlighting their similarities differences. have been shown exert complex effects local inflammation, tumor dynamics, insulin resistance. Significantly, differences cargoes observed among diabetes patients, obese individuals, healthy individuals. These could be used predict development mellitus therapeutic targets for improving sensitivity glucose tolerance. However, further research is needed elucidate underlying mechanisms potential applications AT-exos.

Language: Английский

Context-specific regulation of extracellular vesicle biogenesis and cargo selection DOI
Andrew C. Dixson,

T. Renee Dawson,

Dolores Di Vizio

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(7), P. 454 - 476

Published: Feb. 10, 2023

Language: Английский

Citations

384
A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis DOI Creative Commons
Yongzhi Cui, Yuanyuan Guo, Li Kong

et al.

Bioactive Materials, Journal Year: 2021, Volume and Issue: 10, P. 207 - 221

Published: Sept. 17, 2021

The complex pathogenesis of osteoporosis includes excessive bone resorption, insufficient formation and inadequate vascularization, a combination which is difficult to completely address with conventional therapies. Engineered exosomes carrying curative molecules show promise as alternative therapies, but depend on specifically-functionalized vesicles appropriate engineering strategies. Here, we developed an exosome delivery system based secreted by mesenchymal stem cells (MSCs) derived from human induced pluripotent (iPSCs). engineered BT-Exo-siShn3, took advantage the intrinsic anti-osteoporosis function these special MSC-derived collaborated loaded siRNA Shn3 gene enhance therapeutic effects. Modification bone-targeting peptide endowed BT-Exo-siShn3 ability deliver osteoblasts specifically. Silencing osteoblastic enhanced osteogenic differentiation, decreased autologous RANKL expression thereby inhibited osteoclast formation. Furthermore, silencing increased production SLIT3 consequently facilitated especially type H vessels. Our study demonstrated that could serve promising therapy kill three birds one stone implement comprehensive

Language: Английский

Citations

153
YTHDC1-mediated augmentation of miR-30d in repressing pancreatic tumorigenesis via attenuation of RUNX1-induced transcriptional activation of Warburg effect DOI Creative Commons
Yichao Hou, Qing‐Wei Zhang, Wenjing Pang

et al.

Cell Death and Differentiation, Journal Year: 2021, Volume and Issue: 28(11), P. 3105 - 3124

Published: May 21, 2021

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers. It thrives in a malnourished environment; however, little known about mechanisms by which PDAC cells actively promote aerobic glycolysis to maintain their metabolic needs. Gene Expression Omnibus (GEO) was used identify differentially expressed miRNAs. The expression pattern miR-30d normal and tissues studied situ hybridization. role miR-30d/RUNX1 vitro vivo evaluated CCK8 assay clonogenic formation as well transwell experiment, subcutaneous xenograft model liver metastasis model, respectively. Glucose uptake, ATP lactate production were tested study regulatory effect on cells. Quantitative real-time PCR, western blot, Chip assay, promoter luciferase activity, RIP, MeRIP, RNA stability explore molecular mechanism YTHDC1/miR-30d/RUNX1 PDAC. Here, we discover that remarkably decreased associated with good prognosis, contributed suppression tumor growth metastasis, attenuation Warburg effect. Mechanistically, m 6 A reader YTHDC1 facilitated biogenesis mature via A-mediated regulation mRNA stability. Then, inhibited through regulating SLC2A1 HK1 directly targeting transcription factor RUNX1, bound promoters genes. Moreover, clinically inversely correlated HK1, function adverse prognosis factors for overall survival tissues. Overall, demonstrated functional clinical tumor-suppressive gene Our findings further uncover novel target modification, represses pancreatic tumorigenesis suppressing glycolysis.

Language: Английский

Citations

128
Cancer metabolism and tumor microenvironment: fostering each other? DOI
Yiyuan Yuan, Huimin Li, Pu Wang

et al.

Science China Life Sciences, Journal Year: 2021, Volume and Issue: 65(2), P. 236 - 279

Published: Nov. 26, 2021

Language: Английский

Citations

106
Hypoxic pancreatic cancer derived exosomal miR-30b-5p promotes tumor angiogenesis by inhibiting GJA1 expression DOI Creative Commons
Kai Chen, Qi Wang, Xinxin Liu

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(3), P. 1220 - 1237

Published: Jan. 1, 2022

Purpose: Most patients with pancreatic ductal adenocarcinoma (PDAC) have vascular invasion and metastasis, leading to low surgical resection rate dismal prognosis. Tumor angiogenesis is related metastasis. However, anti-angiogenesis therapeutic effects in PDAC are limited. Therefore, it imperative explore molecular mechanism of PDAC. Experimental Design: scRNA-seq data were utilized delineatetranscriptional profiles endothelial cells The vitro vivo models used the role derived exosomes under hypoxic condition tumor angiogenesis. Results: Endothelial had distinct gene expression compared normal pancreas. marker genes enriched for hypoxia MiR-30b-5p significantly exosomes, which could be transferred HUVEC, resulting upregulation miR-30b-5p. Hypoxic promote tube formation migration via miR-30b-5p mediated downregulation gap junction protein GJA1. Moreover, increased new microvascular density vivo. Patients higher levels total exosomal peripheral blood plasma than healthy subjects. In addition, there significant correlations or between portal vein plasma. Conclusions: promoted by inhibiting GJA1, was a potential diagnostic

Language: Английский

Citations

102
Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications DOI Creative Commons

Yang Qiu-rong,

Jing Xu, Jianmei Gu

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 9(34)

Published: Oct. 17, 2022

Abstract Extracellular vesicles (EVs) are cell‐derived nanosized that mediate cell‐to‐cell communication via transporting bioactive molecules and thus critically involved in various physiological pathological conditions. EVs contribute to different aspects of cancer progression, such as growth, angiogenesis, metastasis, immune evasion, drug resistance. induce the resistance cells chemotherapy, radiotherapy, targeted therapy, antiangiogenesis immunotherapy by transferring specific cargos affect efflux regulate signaling pathways associated with epithelial‐mesenchymal transition, autophagy, metabolism, stemness. In addition, modulate reciprocal interaction between noncancer tumor microenvironment (TME) develop therapy detectable many biofluids patients, regarded novel biomarkers for monitoring response predicting prognosis. Moreover, suggested promising targets engineered nanovehicles deliver drugs overcoming therapy. this review, biological roles their mechanisms action summarized. The preclinical studies on using also discussed.

Language: Английский

Citations

85
miRNAs in pancreatic cancer progression and metastasis DOI Creative Commons
Ellie T. Y. Mok, Jessica L. Chitty, Thomas R. Cox

et al.

Clinical & Experimental Metastasis, Journal Year: 2024, Volume and Issue: 41(3), P. 163 - 186

Published: Jan. 19, 2024

Abstract Small non-coding RNA or microRNA (miRNA) are critical regulators of eukaryotic cells. Dysregulation miRNA expression and function has been linked to a variety diseases including cancer. They play complex role in cancers, having both tumour suppressor promoter properties. In addition, single can be involved regulating several mRNAs many miRNAs regulate mRNA, therefore assessing these roles is essential better understanding cancer initiation development. Pancreatic leading cause death worldwide, part due the lack diagnostic tools limited treatment options. The most common form pancreatic cancer, ductal adenocarcinoma (PDAC), characterised by major genetic mutations that drive progression. regulation interaction with driving suggests strong link between two. Understanding this PDAC progression may give rise novel treatments tools. This review summarises PDAC, downstream signalling pathways they in, how being used studied as therapeutic targets well prognostic/diagnostic improve clinical outcome PDAC.

Language: Английский

Citations

28
Progress in the Understanding of the Mechanism of Tamoxifen Resistance in Breast Cancer DOI Creative Commons

Jingwei Yao,

Kun Deng, Jialu Huang

et al.

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 9, 2020

Tamoxifen is a drug commonly used in the treatment of breast cancer, especially for postmenopausal patients. However, its efficacy limited by development resistance. Downregulation estrogen receptor alpha (ERα) an important mechanism tamoxifen In recent years, with progress research into protective autophagy drug-resistant cells and cell cycle regulators, major breakthroughs have been made on For better understanding resistance, autophagy, some transcription factors enzymes regulating expression are summarized this review. addition, reducing resistance to reviewed. Finally, we discuss possible directions future provide assistance clinical cancer.

Language: Английский

Citations

123
miRNA-Based Technologies in Cancer Therapy DOI Open Access
Maria Pagoni, Claudia Cava, Diamantis C. Sideris

et al.

Journal of Personalized Medicine, Journal Year: 2023, Volume and Issue: 13(11), P. 1586 - 1586

Published: Nov. 9, 2023

The discovery of therapeutic miRNAs is one the most exciting challenges for pharmaceutical companies. Since first miRNA was discovered in 1993, our knowledge biology has grown considerably. Many studies have demonstrated that expression dysregulated many diseases, making them appealing tools novel approaches. This review aims to discuss biogenesis and function, as well highlight strategies delivering agents, presenting viral, non-viral, exosomic delivery approaches different cancer types. We also consider role microRNA-mediated drug repurposing therapy.

Language: Английский

Citations

37
CircEPS15, as a sponge of MIR24-3p ameliorates neuronal damage in Parkinson disease through boosting PINK1-PRKN-mediated mitophagy DOI
Yuanzhang Zhou, Yang Liu,

Zhengwei Kang

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 19(9), P. 2520 - 2537

Published: April 4, 2023

Despite growing evidence that has declared the importance of circRNAs in neurodegenerative diseases, clinical significance dopaminergic (DA) neuronal degeneration pathogenesis Parkinson disease (PD) remains unclear. Here, we performed rRNA-depleted RNA sequencing and detected more than 10,000 plasma samples PD patients. In consideration ROC correlation between Hohen-Yahr stage (H-Y stage) Unified Disease Rating Scale-motor score (UPDRS) 40 patients,

Language: Английский

Citations

29