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HMGA1-mediated miR-671-5p targets APC to promote metastasis of clear cell renal cell carcinoma through Wnt signaling.

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机构: [1]The Affiliated Xiaolan Hospital of Southern Medical University, No. 65 Middle Section of Xiaolan Jucheng Avenue, Zhongshan 528415, China [2]Guangzhou TCM Hospital, No. 16 Zhuji Road, Liwan District, Guangzhou 510515, China [3]Guangdong Second Provincial General Hospital, Courtyard 466 Xingang Middle Road, Haizhu District, Guangzhou 510000, China
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关键词: miR-671-5p APC HMGA1 clear cell renal cell carcinoma

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This study aimed to investigate the effect of miR-671-5p on metastasis of clear cell renal cell carcinoma (ccRCC) and underlying mechanism involved. The migration and invasion of ccRCC cells were determined by transwell and boyden assays in vitro and in vivo. Genes mRNA and protein expression were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The target gene of miRNA was confirmed by luciferase reporter assays. Transcriptional regulation of miRNA by transcription factor was detected by chromatin immunoprecipitation assay (ChIP). The expression of miRNA in clinical specimens were detected by in situ hybridization (ISH). miR-671-5p promoted migration and invasion of ccRCC in vivo and in vitro. Moreover, miR-671-5p directly targeted APC to activate Wnt signaling, thus inducing the epithelial-mesenchymal transition (EMT) in ccRCC. Intriguingly, miR-671-5p expression was transcriptionally enhanced by HMGA1. Consistently, bioinformatics analysis suggested that HMGA1 was positively correlated with miR-671 expression, however, miR-671 was negatively correlated with APC. In situ hybridization analysis showed that miR-671-5p was upregulated in ccRCC compared with paracarcinoma and correlated with poor prognosis of ccRCC patients. In addition, univariate and multivariate analysis indicated that miR-671-5p expression was an independent prognostic factor for overall survival in ccRCC patients. Our data suggest that miR-671-5p is a tumor enhancer in regulating of ccRCC metastasis, and miR-671-5p may be utilized as a factor for the clinical diagnosis and prognosis of ccRCC.

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出版当年[2019]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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第一作者机构: [1]The Affiliated Xiaolan Hospital of Southern Medical University, No. 65 Middle Section of Xiaolan Jucheng Avenue, Zhongshan 528415, China
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