Emerging Function and Clinical Values of Exosomal MicroRNAs in Cancer

Wang, Man; Yu, Fei; Ding, Han; Wang, Yu; Li, Peifeng; Wang, Kun

doi:10.1016/j.omtn.2019.04.027

Cited by 148 publications

(127 citation statements)

References 166 publications

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“…MicroRNAs (miRNAs) are small, endogenous, ncRNAs that modulate target gene expression via interfering with mRNA translation or increasing mRNA degradation and thus exert a prominent biological function in cell proliferation, apoptosis, invasion, differentiation, and other important cellular processes. [14][15][16] Similarly, miRNAs also play a significant regulatory role in ESCC. For instance, miR-134 can restrain ESCC progression via downregulating PLXNA1 to block the MAPK signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

Xu¹,

Xiaojing²,

Li³

et al. 2019

IUBMB Life

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Circular RNAs (circRNAs) are novel noncoding RNAs (ncRNAs) with covalently closed‐loop structures that play an essential regulatory role in diverse malignancies, including esophageal squamous cell cancer (ESCC). Circ_0000654 expression in ESCC and its mechanism of action remains unclear. Real‐time PCR (RT‐PCR) was employed to detect circ_0000654 and miR‐149‐5p expression in ESCC tissues. Circ_0000654 and miR‐149‐5p expression in ESCC cells was selectively regulated. Furthermore, interleukin 6 (IL‐6) and signal transducer and activator of transcription 3 (STAT3) expression in cells was detected by RT‐PCR and western blot analysis, while CCK8, BrdU, flow cytometry, and transwell assays were used to monitor cell proliferation, apoptosis, migration and invasion, respectively. The dual‐luciferase reporter assay and RIP assay were used to verify the targeting relationship between circ_0000654 and miR‐149‐5p, miR‐149‐5p and IL‐6. The function of circ_0000654 on ESCC cell proliferation and metastasis in vivo was examined using a subcutaneous xenograft model and a tail intravenous injection model in nude mice. Circ_0000654 was significantly upregulated in ESCC tissues and cell lines, and its high expression was remarkably associated with an increased T stage and local lymph node metastasis in ESCC patients. Circ_0000654 overexpression and knockdown experiments revealed that circ_0000654 regulated ESCC cell proliferation, migration, invasion, and apoptosis in vitro. Circ_0000654 was identified as a sponge of miR‐149‐5p and facilitated ESCC progression by indirectly activating the IL‐6/STAT3 signaling pathway. Additionally, knocking down circ_0000654 strikingly repressed ESCC growth and metastasis in vivo. In summary, circ_0000654 functions as an oncogenic circRNA in ESCC and accelerates ESCC progression via adsorbing miR‐149‐5p and activating the IL‐6/STAT3 signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

Xu¹,

Xiaojing²,

Li³

et al. 2019

IUBMB Life

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“…Besides, NO, one of the downstream molecular of Akt-endothelial nitric oxide synthase (eNOS) has been testi ed to promote angiogenesis in endothelial cells or others (58,59). It has been recogonized that NO enhances endothelial cell migration, tube formation, and proliferation, and protects endothelial cells from apoptosis [23,24]. Our data found that EC9706 delivered miR-21 led to the increased levels of NO production in recipient HUVEC cells, but we didn't observe a decline of NO levels when incubated with LY294002.…”

Section: Discussionmentioning

confidence: 99%

“…During the progression of the tumor, primary tumor-derived exosomal miRNAs can be transferred to non-malignant cells in the TME to induce heterogeneity (21)(22)(23). At the same time, with the changes in biological activity of non-malignant cells in the TME, nonmalignant cells can also secrete exosomal miRNAs to further regulate tumor cells or other microenvironmental components (24,25). They also mediate in ammatory cell in ltration and immune escape, which is conducive to colonization and proliferation of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Exosome-mediated miR-21 promotes angiogenesis within esophageal tumor microenvironment by activating PTEN/Akt signaling pathway in Vascular Endothelial Cells

Wang¹,

Liao

Yang³

et al. 2020

Preprint

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Background Angiogenesis, a pivotal component in the tumor microenvironment (TME), boosts tumor growth and metastasis. Cancer-derived exosomes, which have been widely reported to play a crucial role in the establishment of TME can be effective angiogenic modulators. We aim to investigate the contribution of microRNA-21 (miR-21) for angiogenesis which was packaged in cancer-derived exosomes in esophageal squamous cell carcinoma (ESCC). Methods The co-cultivation model was constructed to mimic the tumor microenvironment based at a physical level to explore the effects of cancer-derived exosomes on angiogenesis of human umbilical vein endothelial cells (HUVECs). EdU assay, transwell assay and tube formation assay formation experiments were conducted for the evaluation of HUVECs proliferation, migration, and angiogenesis, respectively. In addition, Dual-luciferase reporter (DLR) assay was performed to validate the relationship between miR-21 and its target gene PTEN. Similarly, miR-21 inhibitors and LY294002 was applied to evaluate the regulation of miR-21 via pro-angiogenesis in recipient HUVECs by PTEN/Akt signaling pathway. Results After 24 h co-cultivation with EC9706 cells, miR-21 levels in recipient HUVECs was raised. The results from EdU assay, transwell assay and blood vessel formation experiment showed that exosomes which were secreted from EC9706 cells (EC9706-Exo) delivered miR-21 stimulated proliferation, migration and tube formation of HUVECs. DLR assay indicated that miR-21 could directly bind to the 3'-untranslated region (UTR) of PTEN genes, real-time PCR and western blot analysis for PTEN showed it was inhibited by EC9706-Exo shuttled miR-21. Meanwhile, phospho-Akt (p-Akt) (Ser473), one of the downstream genes of PTEN, was significantly increased in recipient HUVECs compared to the control group, while inhibiting miR-21 and PI3K/Akt pathway respectively both led to a sharp decrease in p-Akt levels, suggesting that exosomal miR-21 promote angiogenesis via activating PTEN/Akt signaling pathway. Conclusion Exosomal miR-21 acts as a driver of pro-angiogenesis by activating PTEN/Akt signaling pathway, it might serve as a blood-based biomarker for ESCC metastasis. Suppressing the expression or blocking the transmission of these exosome-derived miR-21 might be a novel antiangiogenic therapeutic strategy for ESCC.

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“…Cells release a variety of EVs that contain a range of cellular molecules including miRNAs (93). Their ability to transfer miRNAs and mRNAs to recipient cells and influence gene expression was demonstrated in early studies (94)(95)(96), and their role in intercellular communication in cancer is now widely accepted (97). The ability of EVs to deliver miRNAs has subsequently been exploited as a potential vehicle method for miRNA mimics and siRNAs.…”

Section: Alternative Delivery Approachesmentioning

confidence: 99%

Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future

2020

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microRNAs (miRNAs) are an important class of non-coding RNA that post-transcriptionally regulate the expression of most protein-coding genes. Their aberrant expression in tumors contributes to each of the hallmarks of cancer. In malignant pleural mesothelioma (MPM), in common with other tumor types, changes in miRNA expression are characterized by a global downregulation, although elevated levels of some miRNAs are also found. While an increasing number of miRNAs exhibit altered expression in MPM, relatively few have been functionally characterized. Of a growing number with tumor suppressor activity in vitro, miR-16, miR-193a, and miR-215 were also shown to have tumor suppressor activity in vivo. In the case of miR-16, the significant inhibitory effects on tumor growth following targeted delivery of miR-16-based mimics in a xenograft model was the basis for a successful phase I clinical trial. More recently overexpressed miRNAs with oncogenic activity have been described. Many of these changes in miRNA expression are related to the characteristic loss of tumor suppressor pathways in MPM tumors. In this review we will highlight the studies providing evidence for therapeutic effects of modulating microRNA levels in MPM, and discuss these results in the context of emerging approaches to miRNA-based therapy.

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Emerging Function and Clinical Values of Exosomal MicroRNAs in Cancer

Cited by 148 publications

References 166 publications

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

Exosome-mediated miR-21 promotes angiogenesis within esophageal tumor microenvironment by activating PTEN/Akt signaling pathway in Vascular Endothelial Cells

Manipulating microRNAs for the Treatment of Malignant Pleural Mesothelioma: Past, Present and Future

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