MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway

Wang, Lin; Zhou, Rui; Zhao, Yang; Dong, Shaoting; Zhang, Jingwen; Luo, Yuhao; Huang, Na; Shi, Min; Bin, Jianping; Liao, Yulin; Liao, Wangjun

doi:10.1371/journal.pone.0157137

Cited by 19 publications

(22 citation statements)

References 35 publications

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“…Twist1 further promotes tumor cell proliferation, invasion, and resistance to cell death, in addition to enhancing EMT progression and angiogenic development (33)(34)(35). Twist1 upregulation is observed in a variety of cancer types, including OS as well as breast, bladder, gastric, and ovarian cancer (36)(37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1

Zhu

Wang

et al. 2020

Front. Oncol.

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The epithelial-mesenchymal transition (EMT) is a vital step in osteosarcoma (OS) progression toward metastasis, but the specific molecular events governing this process are incompletely characterized, with miRNAs having increasingly been found to regulate the EMT. In this study, We assessed levels of miR-22 and its target, Twist1, via real-time PCR (qRT-PCR). We further used functional proliferation assays, measures of cell morphology, and western blotting to assess the functional relevance of miR-22 in OS and confirmed Twist1 as a miR-22 target via luciferase reporter assay. We observed a significant decrease in miR-22 levels in OS tumor samples relative to normal tissue, with such downregulating being significantly associated with tumor histological grade. When overexpressed, miR-22 impaired OS cell proliferation and EMT progression. We found Twist1 to be a direct miR-22 target, with levels of miR-22 and Twist1 mRNA being inversely correlated in patient samples. When overexpressed, miR-22 suppressed Twist1 translation and thereby attenuated the EMT in OS cells. These results clearly demonstrate that miR-22 can regulate the EMT in OS cells via targeting Twist1, thus highlighting a potentially novel pathway that can be therapeutically targeted in order to treat OS.

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Section: Discussionmentioning

confidence: 99%

Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1

Zhu

Wang

et al. 2020

Front. Oncol.

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“…This is a multistep process involving endothelial cell growth, migration, and capillary tube formation. Vascular endothelial growth factor (VEGF) is a well‐defined angiogenic factor that can be produced by many types of cancer cells such as gastric cancer (Wang et al, ) and hepatocellular carcinoma (Fan et al, ). A number of transcription factors including signal transducer and activator of transcription 3 (STAT3) are implicated in the regulation of VEGF expression (Sarma et al, ).…”

Section: Introductionmentioning

confidence: 99%

C‐X‐C motif chemokine receptor 4 promotes tumor angiogenesis in gastric cancer via activation of JAK2/STAT3

Zhang

Shi

et al. 2017

Cell Biology International

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C-X-C motif chemokine receptor 4 (CXCR4) overexpression promotes gastric cancer growth and metastasis. In this study, we determined its role in regulating tumor angiogenesis. We overexpressed CXCR4 in gastric cancer cells and examined the effects of conditioned medium on endothelial cell proliferation, migration, and tube formation. The effects of CXCR4 overexpression on vascular endothelial growth factor (VEGF) expression and signal transducer and activator of transcription 3 (STAT3) activation were analyzed. In vivo xenograft studies were done to confirm the role of CXCR4 in tumor angiogenesis. Conditioned medium from CXCR4-overexpressing gastric cancer cells stimulated endothelial cell proliferation, migration, and tube formation. Such effects were blocked by addition of a neutralizing anti-VEGF antibody. CXCR4 induced VEGF production and JAK2/STAT3 activation and enhanced STAT3 binding to VEGF promoter in gastric cancer cells. Delivery of a dominant negative variant of STAT3 significantly impaired CXCR4-induced upregulation of VEGF. Overexpression of CXCR4 facilitated tumor growth and angiogenesis in SGC7901 xenograft tumors, which was associated with increased levels of phospho-STAT3. CXCR4 contributes to tumor angiogenesis in gastric cancer by inducing STAT3-dependent VEGF expression and represents a promising therapeutic target for this malignancy.

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“…MACC1 has been established as a key player and biomarker in tumor progression rst in CRC [34] , then across multiple tumor entities [41] . Recent mechanism studies have unveiled possible upstream transcriptional regulation of MACC1 by β-catenin, YB1 [42,43] , while TWIST1/VEGFA, Nanog/Oct4 axis, and SPON2 [44][45][46] as its downstream effectors, hence illustrating a MACC1-centered regulatory network in tumor.…”

Section: Discussionmentioning

confidence: 99%

miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in colorectal cancer

Zhang

Yang

Wang

et al. 2020

Preprint

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Background: It has demonstrated that transcription factors (TFs) could be engaged reciprocal regulative circuits with some miRNAs to maintain the cellular homeostasis. Disequilibrium of the reciprocities by certain tumor-related stimuli, may give rise to deregulation of downstream cellular signaling pathways, thus promoting malignant phenotypes in tumor.Methods: We performed bioinformatics analysis, quantitative polymerase chain reaction (qRT-PCR), immunoblotting, dual-luciferase reporter assay, and a series of functional assays in vitro and in vivo, to describe a novel SP1/miR-320a reciprocal interaction in colorectal cancer (CRC).Results: Firstly, we found that miR-320a was statistically downregulated in CRC tissues and cell lines. Consistent with findings in other cancers, miR-320a exhibited inhibitory effects on cell growth and invasion of CRC in vitro and in vivo. Moreover, we identified Specificity Protein 1 (SP1), a well-known transcription factor, as a target gene of miR-320a, and ectopic SP1 expression partly abolished miR-320a-induced inhibitory effects. Reversely, we confirmed SP1 to interact with miR-320a promoter thus leading to depression of miR-320a. It hence illustrated a double-negative feedback loop engaging miR-320a with SP1. Additionally, on the basis that SP1 promoted MACC1 transcription, we by immunoblotting assay dissect that, the oncogenic signaling MACC1/MET was inactivated in the context of miR-320a-induced SP1 downregulation. Conclusion: Taken together, our study newly describes the miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in CRC, through modulating MACC1/MET signaling pathway.

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MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway

Cited by 19 publications

References 35 publications

Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1

Downregulation of miR-22 Contributes to Epithelial-Mesenchymal Transition in Osteosarcoma by Targeting Twist1

C‐X‐C motif chemokine receptor 4 promotes tumor angiogenesis in gastric cancer via activation of JAK2/STAT3

miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in colorectal cancer

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