Role of exosomal microRNAs in lung cancer biology and clinical applications

Hu, Chengping; Meiners, Silke; Lukas, Christina; Stathopoulos, Georgios T.; Chen, Jie

doi:10.1111/cpr.12828

Cited by 93 publications

(72 citation statements)

References 78 publications

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“…42 For exosomal miRNAs in lung cancer research, Hu et al summarized the exosomal miRNAs in lung cancer as the diagnostic, predictive and prognostic biomarkers. 43 Exosomes isolated from the plasma of 45 non-small cell lung cancer patients and 31 controls were analyzed and indicated that exosomal miR-126 was upregulated and could be the diagnostic biomarker for non-small cell lung cancer. 44 Elevated levels of circulating exosomal miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities, which could also be used as a biomarker for the diagnosis of lung cancer.…”

Section: Contents Of Exosomesmentioning

confidence: 99%

Exosomes: key players in cancer and potential therapeutic strategy

Dai

Zhong

et al. 2020

Sig Transduct Target Ther

733

504

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Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long noncoding RNA, circular RNA, etc., which play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, we mainly summarized as followed: the role of exosome contents in cancer, focusing on proteins and noncoding RNA; the interaction between exosomes and tumor microenvironment; the mechanisms that epithelial-mesenchymal transition, invasion and migration of tumor affected by exosomes; and tumor suppression strategies based on exosomes. Finally, the application potential of exosomes in clinical tumor diagnosis and therapy is prospected, which providing theoretical supports for using exosomes to serve precise tumor treatment in the clinic.

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Section: Contents Of Exosomesmentioning

confidence: 99%

Exosomes: key players in cancer and potential therapeutic strategy

Dai

Zhong

et al. 2020

Sig Transduct Target Ther

733

504

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“…It has been demonstrated that cancer-secreted exosomal miRNAs could be horizontally transferred to the target cells, thereby controlling the biology of cancer cells. 22 For example, exosomal miR-208a from A549 cells, through targeting p21, restrained the proliferation of NSCLC cells via activating the AKT/mechanistic target of rapamycin signaling. 23 Similarly, exos derived from the gemcitabine-resistant A549 cells transferred miR-222-3p to A549 cells and then promoted the proliferation, migration, and invasion of A549 cells by targeting suppressor of cytokine signaling 3.…”

mentioning

confidence: 99%

<p>Hypoxic Non-Small-Cell Lung Cancer Cell-Secreted Exosomal microRNA-582-3p Drives Cancer Cell Malignant Phenotypes by Targeting Secreted Frizzled-Related Protein 1</p>

Wang

Zhao

Zhu

et al. 2020

CMAR

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Background: Hypoxic environment and exosomes (exos)-mediated intercellular communication are crucial for cancer invasion and metastasis, but the mechanisms are not yet fully understood. In this study, we investigated the regulatory effect of hypoxic tumor cell-secreted exosomal miR-582-3p on non-small-cell lung cancer (NSCLC) cell malignant phenotypes. Methods: The concentration and diameters of exos were evaluated by nanosight particle tracking analysis. microRNA-582-3p (miR-582-3p) expression was detected by quantitative real-time PCR. The fluorescent dye PKH26 was used to label exos. The direct interaction between miR-582-3p and secreted frizzled-related protein 1 (SFRP1) was determined by dual-luciferase activity assay. NSCLC cell proliferation, migration, and invasion abilities were assessed by cell count kit-8 assay, wound healing assay, and transwell migration and invasion assay. Western blot analysis was performed to detect the protein expression level. Results: Hypoxic NSCLC cell-derived exos promoted the proliferation, migration, and invasion of normoxic NSCLC cells. miR-582-3p expression was upregulated in hypoxic NSCLC cells and hypoxic NSCLC cell-secreted exos. Hypoxic NSCLC cell-derived exos transmitted miR-582-3p to normoxic NSCLC cells. Hypoxic NSCLC cell-secreted exosomal miR-582-3p promoted the proliferation, migration, and invasion of normoxic NSCLC cells. miR-582-3p inhibited the expression of SFRP1 protein by binding to its 3ʹ-UTR. In addition, enforced expression of SFRP1 restrained malignant phenotypes of normoxic NSCLC cells, which was abrogated by hypoxic NSCLC cell-secreted exosomal miR-582-3p. Conclusion: Hypoxic NSCLC cell-secreted exosomal miR-582-3p drives cancer cell malignant phenotypes by targeting SFRP1, which provides a better understanding of cancer metastasis and may facilitate the development of therapeutics against human NSCLC.

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“…This process is sustained by EVs via delivery and release of their targets into a target cell(s). Alongside tumor progression, EVs have the capability of carrying out other critical processes, including cell proliferation, tumor growth [ 76 ], angiogenesis [ 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ], matrix remodeling, metastasis [ 75 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 ], immune escape [ 69 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ], resistance to apoptosis [ 110 , 111 , 112 , 113 ], deregulation of energetic metabolism [ 114 , 115 , 116 , 117 ], sustaining proliferative signaling [ 94 , 118 , 119 , 120 ], evading growth suppression [ 121 , 122 , 123 ], deregulating and tumor-promoting inflammation [ 100 , 124 , ...…”

Section: Pathological Roles Of Evsmentioning

confidence: 99%

Tiny Actors in the Big Cellular World: Extracellular Vesicles Playing Critical Roles in Cancer

Jurj

Pop-Bica

Slabý

et al. 2020

IJMS

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Communications among cells can be achieved either via direct interactions or via secretion of soluble factors. The emergence of extracellular vesicles (EVs) as entities that play key roles in cell-to-cell communication offer opportunities in exploring their features for use in therapeutics; i.e., management and treatment of various pathologies, such as those used for cancer. The potential use of EVs as therapeutic agents is attributed not only for their cell membrane-bound components, but also for their cargos, mostly bioactive molecules, wherein the former regulate interactions with a recipient cell while the latter trigger cellular functions/molecular mechanisms of a recipient cell. In this article, we highlight the involvement of EVs in hallmarks of a cancer cell, particularly focusing on those molecular processes that are influenced by EV cargos. Moreover, we explored the roles of RNA species and proteins carried by EVs in eliciting drug resistance phenotypes. Interestingly, engineered EVs have been investigated and proposed as therapeutic agents in various in vivo and in vitro studies, as well as in several clinical trials.

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Role of exosomal microRNAs in lung cancer biology and clinical applications

Cited by 93 publications

References 78 publications

Exosomes: key players in cancer and potential therapeutic strategy

Exosomes: key players in cancer and potential therapeutic strategy

<p>Hypoxic Non-Small-Cell Lung Cancer Cell-Secreted Exosomal microRNA-582-3p Drives Cancer Cell Malignant Phenotypes by Targeting Secreted Frizzled-Related Protein 1</p>

Tiny Actors in the Big Cellular World: Extracellular Vesicles Playing Critical Roles in Cancer

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