Circulating exosomal microRNA‐96 promotes cell proliferation, migration and drug resistance by targeting LMO7

Wu, Hao; Zhou, Jingcheng; Mei, Shanshan; Wu, Der-Min; Mu, Zhimin; Chen, Baokun; Xie, Yu; Ye, Yiwang; Liu, Jixian

doi:10.1111/jcmm.13056

Cited by 134 publications

(103 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5E, F). This suppression of cell proliferation was contradictory to the prevalently reported pro-proliferative effect of cancer exosomes 15,[35][36][37][38][39] . We assessed the expressions of six cyclins (CCNA1, CCNA2, CCND1, CCND2, CCND3, CCNE2), five cyclin-dependent kinase (CDK1, CDK2, CDK4, CDK6, CDK7) and eight cyclin-dependent kinase inhibitors (CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CDKN3) in HUVECs.…”

Section: Mda231-hexos Promoted Vegfr-dependent Angiogenesiscontrasting

confidence: 75%

Cancer exosomes harbor diverse hypoxia-targeted mRNAs and contribute toward tumor angiogenesis

Zhang

Lim

Jiang

et al. 2020

Preprint

View full text Add to dashboard Cite

Exosomes are extracellular vesicles of endosome origin secreted by various cells. The exosomal cargo, especially proteins and microRNAs, have been extensively investigated for their roles in intercellular communication and as biomarkers for clinical applications. However, the understanding of types and functions of exosomal mRNAs remains limited. Here, we evaluated the mRNAs of 61 hypoxia-targeted genes in exosomes by quantitative reverse transcription PCR (RT-qPCR). Among these 61 mRNAs, 14.8% of them were detected in the MCF10A-derived exosomes, 42.6% in the MCF7-derived exosomes, and 49.2% in the MDA-MB-231-derived exosomes, many of which are differentially regulated in response to hypoxic stress in a cell-line dependent manner. Consequently, 30 exosomal mRNAs are identified as cancer related biomarkers as they are present in cancer cell-derived exosomes and absent in MCF10A-derived exosomes. Co-culture of MDA-MB-231 cells with HUVECs shows uptake of MDA-MB-231 secreted exosomes by the Human umbilical vein endothelial cells (HUVECs). Subsequently, the cancer exosomal VEGFA mRNAs were translated within the HUVECs into proteins that promoted VEGFR-dependent angiogenesis. This finding provides novel insights into how cancer cells can directly contribute towards angiogenesis. RNA-seq also shows that cancer exosomes can upregulate epithelial-mesenchymal transition-related and metabolism-related genes. The transcripts of these genes are found present in the cancer exosomes, suggesting that the uptake of exosomal mRNAs at least partially contributed to the upregulation of the corresponding mRNAs. This study shows that cancer exosomes harbor diverse mRNAs, some of which can act as promising biomarkers as well as contribute towards reprogramming of recipient cells.

show abstract

Section: Mda231-hexos Promoted Vegfr-dependent Angiogenesiscontrasting

confidence: 75%

Cancer exosomes harbor diverse hypoxia-targeted mRNAs and contribute toward tumor angiogenesis

Zhang

Lim

Jiang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Exosomes are a type of nanosized membrane-derived vesicle secreted by cells. 9–12 Exosomes are specifically loaded with cargo proteins and functional RNA molecules 12–15 and released into the extracellular space upon fusion with the plasma membrane. Their secretion has been observed from all types of normal and tumor cells, where they carry various cellular proteins throughout the body and act as a means of intercellular communication to transport signals to other organs.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Proteomic Analysis of Serum Exosomes from Patients with Locally Advanced Pancreatic Cancer Undergoing Chemoradiotherapy

Lohse

Tan

et al. 2017

J. Proteome Res.

View full text Add to dashboard Cite

Pancreatic cancer is the third leading cause of cancer-related death in the USA. Despite extensive research, minimal improvements in patient outcomes have been achieved. Early identification of treatment response and metastasis would be valuable to determine the appropriate therapeutic course for patients. In this work, we isolated exosomes from the serum of 10 patients with locally advanced pancreatic cancer at serial time points over a course of therapy, and quantitative analysis was performed using the iTRAQ method. We detected approximately 700–800 exosomal proteins per sample, several of which have been implicated in metastasis and treatment resistance. We compared the exosomal proteome of patients at different time points during treatment to healthy controls and identified eight proteins that show global treatment-specific changes. We then tested the effect of patient-derived exosomes on the migration of tumor cells and found that patient-derived exosomes, but not healthy controls, induce cell migration, supporting their role in metastasis. Our data show that exosomes can be reliably extracted from patient serum and analyzed for protein content. The differential loading of exosomes during a course of therapy suggests that exosomes may provide novel insights into the development of treatment resistance and metastasis.

show abstract

“…miRNA‐155 in EVs from gemcitabine‐resistant pancreatic cancer cells can induce resistance when taken up by sensitive recipient cells; miR‐155 induces this resistance by targeting the pro‐apoptotic gene TP53INP1 . Transfer of miR‐96 in lung cancer cells (from H1299 to A549 cells) may cause resistance to cisplatin that is mediated by targeting of the LIM‐domain only protein 7 . Another study with the same pair of cells showed that transfer of miR‐222 may be involved in mediating resistance to adriamycin .…”

Section: Transfer Of Ev Rna Can Cause Transfer Of Drug Resistancementioning

confidence: 99%

Mechanisms of Drug Resistance in Cancer: The Role of Extracellular Vesicles

2017

View full text Add to dashboard Cite

Drug resistance remains a major barrier to the successful treatment of cancer. The mechanisms by which therapeutic resistance arises are multifactorial. Recent evidence has shown that extracellular vesicles (EVs) play a role in mediating drug resistance. EVs are small vesicles carrying a variety of macromolecular cargo released by cells into the extracellular space and can be taken up into recipient cells, resulting in transfer of cellular material. EVs can mediate drug resistance by several mechanisms. They can serve as a pathway for sequestration of cytotoxic drugs, reducing the effective concentration at target sites. They can act as decoys carrying membrane proteins and capturing monoclonal antibodies intended to target receptors at the cell surface. EVs from resistant tumor cells can deliver mRNA, miRNA, long noncoding RNA, and protein inducing resistance in sensitive cells. This provides a new model for how resistance that arises can then spread through a heterogeneous tumor. EVs also mediate cross-talk between cancer cells and stromal cells in the tumor microenvironment, leading to tumor progression and acquisition of therapeutic resistance. In this review, we will describe what is known about how EVs can induce drug resistance, and discuss the ways in which EVs could be used as therapeutic targets or diagnostic markers for managing cancer treatment. While further characterization of the vesiculome and the mechanisms of EV function are still required, EVs offer an exciting opportunity in the fight against cancer.

show abstract

Circulating exosomal microRNA‐96 promotes cell proliferation, migration and drug resistance by targeting LMO7

Cited by 134 publications

References 33 publications

Cancer exosomes harbor diverse hypoxia-targeted mRNAs and contribute toward tumor angiogenesis

Cancer exosomes harbor diverse hypoxia-targeted mRNAs and contribute toward tumor angiogenesis

Quantitative Proteomic Analysis of Serum Exosomes from Patients with Locally Advanced Pancreatic Cancer Undergoing Chemoradiotherapy

Mechanisms of Drug Resistance in Cancer: The Role of Extracellular Vesicles

Contact Info

Product

Resources

About