Exosomal microRNAs (exomiRs): Small molecules with a big role in cancer

Bhome, Rahul; Vecchio, Filippo Del; Lee, Gui-Han; Bullock, Marc D.; Primrose, John; Sayan, Emre; Mirnezami, Alex H.

doi:10.1016/j.canlet.2018.02.002

Cited by 187 publications

(143 citation statements)

References 96 publications

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“…This finding is consistent with other reported research that EVs may transport largely mRNA fragments to recipient cells 75,76 , which may indicate a novel mechanism along with miRNAs for genetic exchange between cells 19 . It is worth mentioning that EV miRNA contents from cervical cancer patient plasma are clearly higher than the healthy individual (3:1), which is consistent with majority reports that miRNAs were significantly enriched in EVs as the important diagnostic markers for cancer [77][78][79] . The next-generation RNA-Seq profiling of EV miRNAs from biopsy specimens is a relatively underexplored frontier.…”

Section: The 3d Cell Culture Derived Ev Rna Profile Shows a Significasupporting

confidence: 89%

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Thippabhotla

Wei

Zhong

et al. 2019

Preprint

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For studying cellular communications ex-vivo, a two-dimensional (2D) cell culture model is currently used as the "gold standard". 2D culture models are also widely used in the study of RNA expression profiles from tumor cells secreted extracellular vesicles (EVs) for tumor biomarker discovery. Although the 2D culture system is simple and easily accessible, the culture environment is unable to represent in vivo extracellular matrix (ECM) microenvironment. Our study observed that 2D culture-derived EVs showed significantly different profiles in terms of secretion dynamics and essential signaling molecular contents (RNAs and DNAs), when compared to the three-dimensional (3D) culture-derived EVs. By performing small RNA next-generation sequencing (NGS) analysis of cervical cancer cells and their EVs compared with cervical cancer patient plasma EV-derived small RNAs, we observed that 3D culture-derived EV small RNAs differ from their parent cell small RNA profile which may indicate a specific sorting process. Most importantly, the 3D culture derived EV small RNA profile exhibited a much higher similarity (~96%) to in vivo circulating EVs derived from cervical cancer patient plasma. However, 2D culture derived EV small RNA profile correlated better with only their parent cells cultured in 2D. On the other hand, DNA sequencing analysis suggests that culture and growth conditions do not affect the genomic information carried by EV secretion. This work also suggests that tackling EV molecular alterations secreted into interstitial fluids can provide an alternative, non-invasive approach for investigating 3D tissue behaviors at the molecular precision. This work could serve as a foundation for building precise models employed in mimicking in vivo tissue system with EVs as the molecular indicators or transporters. Such models could be used for investigating tumor biomarkers, drug screening, and understanding tumor progression and metastasis.

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Section: The 3d Cell Culture Derived Ev Rna Profile Shows a Significasupporting

confidence: 89%

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Thippabhotla

Wei

Zhong

et al. 2019

Preprint

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“…Notably, exosomes derived from MSCs enhance radiotherapy‐induced cell death in tumor and metastatic tumor foci . Especially, exosomal miRNAs are highly suitable candidates for use as biomarkers in personalized cancer medicine . Actually, stem cell‐secreted exosomes orchestrate various autocrine and paracrine functions which alter tumor microenvironment, growth and progression .…”

Section: Disccussionmentioning

confidence: 99%

Exosomal miRNA‐1231 derived from bone marrow mesenchymal stem cells inhibits the activity of pancreatic cancer

et al. 2019

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Pancreatic cancer (PC) is a highly malignant tumor with increased morbidity and mortality, which is difficult to diagnose and cure in the clinic. Through secreting exosomes containing biological molecules, including diverse RNAs and proteins, bone marrow mesenchymal stem cells (BM‐MSCs) influence the immunity, inflammation, tumor environment, and cancer metastasis. In this study, low expression of miRNA‐1231 (miR‐1231) in exosomes derived from the peripheral blood was significantly correlated with the TNM stage of PC, suggesting the potential inhibitory effect of exosomal miR‐1231 on PC occurrence and development. The proliferation, migration, invasion, and adhesion to the matrix of PC cells BxPC‐3 and PANC‐1 were negatively regulated by exosomes derived from the supernatants of BM‐MSCs that transfected with miR‐1231 oligonucleotides. Simultaneously, tumor growth in vivo was seriously restrained in BALB/C nude mice by tail vein injection with exosomes originated from BM‐MSCs that transfected with miR‐1231 mimics. The exosomes extracted from BM‐MSCs with high level of miR‐1231 inhibit the activity of PC, providing the potential application for developing new and efficient medicine for cancer therapy, especially for PC treatment. The exosomal miR‐1231 of peripheral blood may also be a potential indicator for PC diagnosis in the future.

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“…The role of EVs is not only in cell–cell communication (Saeed‐Zidane et al, ) but also in the removal of undesirable cellular molecules (Takahashi et al, ). Contrary to cellular expression, the NOTCH1 was increased in EVs derived from male embryos exposed to OS compared with female counterparts, which may indicate the selectivity of cargo molecules to be exported by EVs (Bhome et al, ; Hinger et al, ) to facilitate cell to cell communication or maintain of cellular homeostasis. Herein, we can summarize that exposing preimplantation bovine embryos to OS compromised the transformation of blastocysts irrespective of embryo sex, due to increasing intracellular ROS accumulation, which in turn leads to increase apoptosis and delay of differentiation in response to dysregulating of the TFs related to stress response, development, differentiation, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Sexual dimorphic expression and release of transcription factors in bovine embryos exposed to oxidative stress

Taqi

Saeed‐Zidane

Gebremedhn

et al. 2019

Molecular Reproduction Devel

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Sexually dimorphic differences in genome activity, which is orchestrated by transcription factors (TFs), could explain the differential response of male and female embryos to environmental stressors. To proof this hypothesis, the expression of cellular and extracellular TFs was investigated in male and female bovine embryos in vitro cultured either under low (5%) or high (20%) oxygen levels. The intracellular reactive oxygen species (ROS), total cell number, expression of nuclear factor (erythroid‐derived 2) factor 2 (NFE2L2), Krüppel‐like factor 4 (KLF4), notch receptor 1 (NOTCH1), E2F transcription factor 1 (E2F1), and SREBF2 along with extracellular vesicles (EVs) biogenesis genes were assessed at the blastocyst stage and their released EVs. Low blastocyst rate in both sexes due to oxidative stress (OS) was accompanied by increased ROS accumulation and reduced cell number in female embryos. The messenger RNA and protein levels of NFE2L2, as well as KLF4 expression, were higher in male embryos exposed to OS compared with female embryos. However, the expression of NOTCH1 and E2F1 was higher in female embryos cultured in high oxygen level. Male embryos exposed to OS released more EVs enriched with NFE2L2, superoxide dismutase 1, and NOTCH1 accompanied by elevated expression of EVs biogenesis genes. Accordingly, differential expression of TFs and their release into spent media could partially explain the sexual dimorphic response of bovine embryos to environmental stresses.

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Exosomal microRNAs (exomiRs): Small molecules with a big role in cancer

Cited by 187 publications

References 96 publications

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Exosomal miRNA‐1231 derived from bone marrow mesenchymal stem cells inhibits the activity of pancreatic cancer

Sexual dimorphic expression and release of transcription factors in bovine embryos exposed to oxidative stress

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