Hypoxic gastric cancer-derived exosomes promote progression and metastasis via MiR-301a-3p/PHD3/HIF-1α positive feedback loop

Xia, Xiang; Wang, Shuchang; Ni, Bo; Xing, Shunpeng; Cao, Hui; Zhang, Zizhen; Yu, Fengrong; Zhao, Enyue; Zhao, Gang

doi:10.1038/s41388-020-01425-6

Cited by 89 publications

(73 citation statements)

References 45 publications

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“…This leads to hypoxia-inducible factor-1α (HIF-1α) accumulation in endothelial cells, which promotes the formation and permeability of blood vessels, as well as tumor migration ( 62 ). Moreover, hypoxia also increases gastric cancer (GC) exosome release and miR-301α-3p expression in a HIF-1α-dependent manner, which promotes GC progression and metastasis ( 63 ). The expression level of miR-103 of exosomes in highly invasive HCC cells is significantly higher compared with that in non-metastatic HCC cells.…”

Section: Exosomes Promote Tumor Metastasismentioning

confidence: 99%

Roles of exosomes in cancer chemotherapy resistance, progression, metastasis and immunity, and their clinical applications (Review)

2021

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Exosomes are a type of vesicle that are secreted by cells, with a diameter of 40-100 nm, and that appear as a cystic shape under an electron microscope. Exosome cargo includes a variety of biologically active substances such as non-coding RNA, lipids and small molecule proteins. Exosomes can be taken up by neighboring cells upon secretion or by distant cells within the circulatory system, affecting gene expression of the recipient cells. The present review discusses the formation and secretion of exosomes, and how they can remodel the tumor microenvironment, enhancing cancer cell chemotherapy resistance and tumor progression. Exosome-mediated induction of tumor metastasis is also highlighted. More importantly, the review discusses the manner in which exosomes can change the metabolism of cancer cells and the immune system, which may help to devise novel therapeutic approaches for cancer treatment. With the development of nanotechnology, exosomes can also be used as biomarkers and for the delivery of chemical drugs, serving as a tool to diagnose and treat cancer.

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Section: Exosomes Promote Tumor Metastasismentioning

confidence: 99%

Roles of exosomes in cancer chemotherapy resistance, progression, metastasis and immunity, and their clinical applications (Review)

2021

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“…Zhang et al revealed that miR-10b-5p, miR-101-3p, and miR-143-5p could be used as biomarkers for GC patients with lymph node metastasis, ovarian metastasis, and liver metastasis, respectively (AUC values of 0.8919, 0.8905, and 0.8247) (155). In addition, Xia et al found that the serum exosomal miR-301a-3p is positively correlated with peritoneal metastasis (63).…”

Section: Prognostic Biomarkersmentioning

confidence: 99%

“…In addition, recent studies have found that GC cells can produce exosomes that are rich in miR-301a-3p in the hypoxic TME. For example, exosomal miR-301a-3p can be transmitted between GC cells to inhibit HIF-1α degradation by targeting PHD3, thereby promoting the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of GC ( 63 ). At present, the role of miR-221 in promoting tumor cell proliferation, migration, and drug resistance has been widely recognized ( 94 , 95 ).…”

Section: Biological Functions Of Exosomal Ncrnas In Gcmentioning

confidence: 99%

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Role of Exosomal Non-coding RNAs in Gastric Cancer: Biological Functions and Potential Clinical Applications

Liu

et al. 2021

Front. Oncol.

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Gastric cancer (GC) is one of the most common fatal cancers worldwide. The communication between GC and other cells in the GC microenvironment directly affects GC progression. Recently, exosomes have been revealed as new players in intercellular communication. They play an important role in human health and diseases, including cancer, owing to their ability to carry various bioactive molecules, including non-coding RNAs (ncRNAs). NcRNAs, including micro RNAs, long non-coding RNAs, and circular RNAs, play a significant role in various pathophysiological processes, especially cancer. Increasing evidence has shown that exosomal ncRNAs are involved in the regulation of tumor proliferation, invasion, metastasis, angiogenesis, immune regulation, and treatment resistance in GC. In addition, exosomal ncRNAs have promising potential as diagnostic and prognostic markers for GC. Considering the biocompatibility of exosomes, they can also be used as biological carriers for targeted therapy. This review summarizes the current research progress on exosomal ncRNAs in gastric cancer, focusing on their biological role in GC and their potential as new biomarkers for GC and therapeutics. Our review provides insight into the mechanisms involved in GC progression, which may provide a new point cut for the discovery of new diagnostic markers and therapeutic strategies.

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“…However, current research has not fully explained the interaction mechanism between HIF and other molecules. For example, a recent study found that in hypoxic TME, enriched miR-301a-3p could be transmitted between GC cells via exosomes and then contributed to inhibit HIF-1α degradation through targeting PHD3 [45]. This means that extracellular vesicles (EVs) with proteins or RNA can regulate the stability of HIF in tumor cells.…”

Section: The Canonical Pathway Of Phd-mediated Regulation Of Hifmentioning

confidence: 99%

Autonomous glucose metabolic reprogramming of tumour cells under hypoxia: opportunities for targeted therapy

Huang

Yang

Peng

et al. 2020

J Exp Clin Cancer Res

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Molecular oxygen (O2) is a universal electron acceptor that is eventually synthesized into ATP in the mitochondrial respiratory chain of all metazoans. Therefore, hypoxia biology has become an organizational principle of cell evolution, metabolism and pathology. Hypoxia-inducible factor (HIF) mediates tumour cells to produce a series of glucose metabolism adaptations including the regulation of glucose catabolism, glycogen metabolism and the biological oxidation of glucose to hypoxia. Since HIF can regulate the energy metabolism of cancer cells and promote the survival of cancer cells, targeting HIF or HIF mediated metabolic enzymes may become one of the potential treatment methods for cancer. In this review, we summarize the established and recently discovered autonomous molecular mechanisms that can induce cell reprogramming of hypoxic glucose metabolism in tumors and explore opportunities for targeted therapy.

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Hypoxic gastric cancer-derived exosomes promote progression and metastasis via MiR-301a-3p/PHD3/HIF-1α positive feedback loop

Cited by 89 publications

References 45 publications

Roles of exosomes in cancer chemotherapy resistance, progression, metastasis and immunity, and their clinical applications (Review)

Roles of exosomes in cancer chemotherapy resistance, progression, metastasis and immunity, and their clinical applications (Review)

Role of Exosomal Non-coding RNAs in Gastric Cancer: Biological Functions and Potential Clinical Applications

Autonomous glucose metabolic reprogramming of tumour cells under hypoxia: opportunities for targeted therapy

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