Dataset Information

DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting ?-catenin Signaling to Induce Expression of VEGFA.

ABSTRACT: We previously reported that overexpression of DHX32 contributes to the growth and metastasis of colorectal cancer (CRC). However, the underlying mechanism is not largely characterized. Herein, we reported that DHX32 in CRC cells upregulated expression of vascular endothelial growth factor A (VEGFA) at the transcription level through interacting with and stabilizing ?-catenin. This promoted the recruitment of host endothelial cells to the tumor, and therefore, formation of microvessel in the tumor. Xenograft model revealed that depletion of DHX32 in CRC cells significantly reduced the microvessel density in the grafts and suppressed the growth of grafts. Furthermore, the expression level of DHX32 was positively associated with microvessel density in human CRC and poor outcome of CRC patients. Therefore, the report demonstrates that DHX32 is a pro-angiogenic factor, that inhibition of DHX32-?-catenin pathway can provide a strategy for CRC treatment, and that the expression level of DHX32 has the potential to serve as a biomarker for CRC diagnosis and prognosis.

SUBMITTER: Lin H

PROVIDER: S-EPMC5405167 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting β-catenin Signaling to Induce Expression of VEGFA.

Lin Huayue H Fang Zanxi Z Su Yuanhui Y Li Peihua P Wang Jingkun J Liao Hongfeng H Hu Qing Q Ye Chunlei C Fang Yizhen Y Luo Qing Q Lin Zhiyuan Z Pan Chao C Wang Fen F Zhang Zhong-Ying ZY

EBioMedicine 20170309

We previously reported that overexpression of DHX32 contributes to the growth and metastasis of colorectal cancer (CRC). However, the underlying mechanism is not largely characterized. Herein, we reported that DHX32 in CRC cells upregulated expression of vascular endothelial growth factor A (VEGFA) at the transcription level through interacting with and stabilizing β-catenin. This promoted the recruitment of host endothelial cells to the tumor, and therefore, formation of microvessel in the tumo ...[more]

PMID: 28330603

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Project description:PurposeAngiogenesis actively contributes to tumor growth and metastasis. MACC1 was reported to be associated with tumor progression. In the present study, we aimed to investigate the expression and role of MACC1 in cholangiocarcinoma (CCA) and its correlation with angiogenesis.Patients and methodsWe investigated the expression and correlation of MACC1 and VEGFA in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and in 7 paired frozen CCA and matched paracarcinoma tissues. Immunohistochemistry (IHC) was used to examine MACC1 and VEGFA expression as well as microvessel density (MVD) in 122 paraffin-embedded CCA samples. Western blotting, real-time qPCR and ELISA were performed to investigate the effect of MACC1 knockdown on VEGFA expression and secretion in CCA cells. Subsequently, we collected conditioned medium from cells with MACC1 knockdown and used it in angiogenesis assays.ResultsThe expression levels of both MACC1 and VEGFA were significantly upregulated in the TCGA and GEO datasets and in the 7 paired frozen CCA tissues compared to the matched paracarcinoma tissues, and MACC1 was significantly correlated with VEGFA. IHC showed that high expression of MACC1 and VEGFA was significantly correlated with lymph node metastasis (P<0.05 and P<0.01) and worse survival (P<0.01, P<0.05) in patients with CCA. We further verified that MACC1 was significantly correlated with VEGFA (P<0.01) and MVD (P<0.01) in clinical samples. Western blotting, real-time qPCR and ELISA results showed that MACC1 knockdown in CCA cells significantly decreased the protein and mRNA expression of VEGFA and reduced the VEGFA concentration in conditioned medium. Moreover, angiogenesis assays showed that conditioned medium from CCA cells with MACC1 knockdown decreased the number of tubes formed.ConclusionOur results indicate that MACC1 and VEGFA expression are upregulated in CCA. Moreover, MACC1 is an independent predictor of overall survival and facilitates angiogenesis in CCA by upregulating of VEGFA.

Dataset Information

DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting ?-catenin Signaling to Induce Expression of VEGFA.

Publications

DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting β-catenin Signaling to Induce Expression of VEGFA.

Similar Datasets

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