VEGFA links self-renewal and metastasis by inducing Sox2 to repress miR-452, driving Slug

Kim, M.; Jang, Keum‐Il; Miller, Philip; Picón-Ruiz, Manuel; Yeasky, Toni M.; El-Ashry, Dorraya; Slingerland, Joyce M.

doi:10.1038/onc.2017.4

Cited by 90 publications

(64 citation statements)

References 99 publications

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“… 22 , 23 In addition, VEGFA has been found to contribute to tumor growth and metastasis by inducing angiogenesis via the VEGFR-1 and VEGFR-2. 21 , 22 , 24 In TC, VEGFA expression was increased in the TC tissues, and overexpression of VEGFA was correlated with the pathologic parameters and metastatic status of the thyroid carcinomas. 25 , 26 In this study, we identified VEGFA as a target of miR-622 in TC.…”

Section: Discussionmentioning

confidence: 96%

miR-622 suppresses tumor formation by directly targeting VEGFA in papillary thyroid carcinoma

Wang

et al. 2018

OTT

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BackgroundMicroRNAs (miRNAs) were reportedly to play crucial roles in papillary thyroid carcinoma (PTC) tumorigenesis and development. Therefore, the discovery of miRNAs may provide a new and powerful tool for diagnosis and treatment of PTC.PurposeThe aim of this study was to investigate the biological function and underlying mechanism of miR-622 in PTC.Materials and methodsThe expression levels of miR-622 in PTC patient tissues and cell lines were determined by quantitative RT-PCR (qRT-PCR). The biological function including cell proliferation, colony formation, migration and invasion, as well as underling mechanism of miR-622 in PTC, were also evaluated by a series of in vitro and in vivo experiments.ResultsmiR-622 expression level was significantly downregulated in PTC tissues and cell lines. Decreased miR-622 expression was associated with advanced clinical stage and lymph node metastasis (P<0.01). The overexpression of miR-622 in TPC-1 cells inhibited cell proliferation, migration and invasion in vitro, as well as suppress tumor growth in vivo. Moreover, we also demonstrated that miR-622 specifically targeted the 3′-UTR regions of vascular endothelial growth factor A (VEGFA) and inhibited its expression both mRNA level and protein levels. Overexpression of VEGFA reversed miR-622-mediated inhibition effect on cell proliferation, migration and invasion in thyroid cancer cells. More importantly, VEGFA expression was significantly increased and inversely correlated with the levels of miR-622 in PTC tissues.ConclusionThese results show that miR-622 acts as a tumor suppressor in thyroid cancer, at least in part, via targeting VEGFA, and suggest that miR-622 may serves as a potential target for treatment of thyroid cancer patients.

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Section: Discussionmentioning

confidence: 96%

miR-622 suppresses tumor formation by directly targeting VEGFA in papillary thyroid carcinoma

Wang

et al. 2018

OTT

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“…Similarly, the high level of ZEB1, another EMT-related transcription factor, was strongly associated with the presence of VM in 96 prostate cancer samples (P < 0.05) 37. In breast cancer, VEGFA led to EMT by up-regulating SOX2 expression in vivo and in vitro 39. VEGFA could stimulate EMT of pancreatic neuroendocrine tumour cells in vitro 38.…”

mentioning

confidence: 91%

“…VEGFA could stimulate EMT of pancreatic neuroendocrine tumour cells in vitro 38. In breast cancer, VEGFA led to EMT by up-regulating SOX2 expression in vivo and in vitro 39. VEGFA could sustain EMT in sonic hedgehog medulloblastoma stem cells via Nrp2 40.…”

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confidence: 95%

Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma

Wang

Zheng

et al. 2019

Cell Proliferation

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Objectives To investigate the role of hypoxia in vasculogenic mimicry (VM) of salivary adenoid cystic carcinoma (SACC) and the underlying mechanism involved. Materials and methods Firstly, wound healing, transwell invasion, immunofluorescence and tube formation assays were performed to measure the effect of hypoxia on migration, invasion, EMT and VM of SACC cells, respectively. Then, immunofluorescence and RT‐PCR were used to detect the effect of hypoxia on VE‐cadherin and VEGFA expression. And pro‐vasculogenic mimicry effect of VEGFA was investigated by confocal laser scanning microscopy and Western blot. Moreover, the levels of E‐cadherin, N‐cadherin, Vimentin, CD44 and ALDH1 were determined by Western blot and immunofluorescence in SACC cells treated by exogenous VEGFA or bevacizumab. Finally, CD31/ PAS staining was performed to observe VM and immunohistochemistry was used to determine the levels of VEGFA and HIF‐1α in 95 SACC patients. The relationships between VM and clinicopathological variables, VEGFA or HIF‐1α level were analysed. Results Hypoxia promoted cell migration, invasion, EMT and VM formation, and enhanced VE‐cadherin and VEGFA expression in SACC cells. Further, exogenous VEGFA markedly increased the levels of N‐cadherin, Vimentin, CD44 and ALDH1, and inhibited the expression of E‐cadherin, while the VEGFA inhibitor reversed these changes. In addition, VM channels existed in 25 of 95 SACC samples, and there was a strong positive correlation between VM and clinic stage, distant metastases, VEGFA and HIF‐1α expression. Conclusions VEGFA played an important role in hypoxia‐induced VM through regulating EMT and stemness, which may eventually fuel the migration and invasion of SACC.

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“…VEGFA mainly functions by binding to the receptors, especially VEGFR2, and activates the VEGFR2-dependent signaling pathways 41 . Moreover, VEGFA can accelerate tumor progression by promoting EMT and metastasis 42 . In patients with colorectal cancer liver metastasis, VEGFA could be a prognostic biomarker 43 .…”

Section: Discussionmentioning

confidence: 99%

Circ_0030998 Promotes Tumor Proliferation and Angiogenesis by Sponging miR-567 to Regulate VEGFA in Colorectal Cancer

Jin

Chen

Zhai

et al. 2020

Preprint

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BackgroundColorectal cancer (CRC) is one of the most common malignancies worldwide. Accumulating studies have demonstrated that circular RNAs (circRNAs), a novel class of noncoding RNAs, are involved in pathological processes, especially in the development of cancers. But the roles of circRNAs in CRC are largely unknown.MethodsThe microarray data GSE138589 was analyzed and qRT-PCR was performed to screen out the circRNA with the highest upregulated level in CRC. QRT-PCR was used to determine the expression of genes in different tissues or cells. RNA-FISH was conducted to identify the subcellular localization of Circ_0030998. In vitro and in vivo assays were performed to determine the effect of Circ_0030998 on the CRC cells proliferation and angiogenesis. The relationships of Circ_0030998, miR-567 and VEGFA were predicted and validated using bioinformatic tools, RIP and luciferase assays.ResultsWe identified a novel circRNA, Circ_0030998, was upregulated in CRC tissues and cells, and its upregulation was related with poor prognosis in CRC patients. Circ_0030998 promoted CRC cells proliferation and angiogenesis. RNA-FISH showed that Circ_0030998 was mainly localized in the cytoplasm of CRC cells. Mechanistic studies demonstrated that Circ_0030998 acted as a miR-567 sponge to relieve its inhibitory effect on VEGFA. Rescue assays validated that Circ_0030998 functioned in CRC cells proliferation and angiogenesis relying on VEGFA.ConclusionsThe present study clarified the Circ_0030998/miR-567/VEGFA regulation axis and indicated that Circ_0030998 could be a potential therapeutic target for CRC.

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VEGFA links self-renewal and metastasis by inducing Sox2 to repress miR-452, driving Slug

Cited by 90 publications

References 99 publications

miR-622 suppresses tumor formation by directly targeting VEGFA in papillary thyroid carcinoma

miR-622 suppresses tumor formation by directly targeting VEGFA in papillary thyroid carcinoma

Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma

Circ_0030998 Promotes Tumor Proliferation and Angiogenesis by Sponging miR-567 to Regulate VEGFA in Colorectal Cancer

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