关键词: Alternative splicing DAZAP1 Hepatocellular carcinoma Tumor growth

Mesh : Carcinoma, Hepatocellular / diagnostic imaging genetics metabolism pathology Cell Line Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Humans Liver Neoplasms / diagnostic imaging genetics metabolism pathology Prognosis RNA-Binding Proteins / biosynthesis genetics metabolism Ultrasonography

来  源:   DOI:10.1007/s12094-021-02758-8

Abstract:
OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common types of hepatic carcinoma. The overall prognosis is poor. DAZAP1, a regulator of alternative splicing (AS) events, may participate in tumor growth.
METHODS: We collected 105 HCC patients and tissue samples from the Department of Hepatological Surgery in the Second Affiliated Hospital of Qiqihar Medical University. TCGA datasets were downloaded and operated using the R project. DAZAP1 expressions were examined by quantitative RT-PCR and western blotting. CCK8 assay was used to investigate the cell proliferation, and transwell assay was employed to examine the ability of migration and invasion in vitro. Contrast-enhanced ultrasound (CEUS) was used to evaluate images and parameters of the tumor.
RESULTS: DAZAP1 is highly expressed in the tissue samples of HCC. The peak intensity (PI) and area under the curve (AUC) of the tumor is higher than that of liver parenchyma, and correlated with high DAZAP1 expression. Parameters of CEUS in the tumor are correlated with TNM stage, tumor size, and vascularity. High DAZAP1 expression correlates with a shorter survival time and advanced histologic grade (G3-G4). Bioinformatical analysis revealed that downregulation of DAZAP1 identified differentiated expressed genes (DEGs) involved in the tumor growth process.
CONCLUSIONS: DAZAP1 is highly expressed in hepatic carcinoma and related to the blood flow, and high DAZAP1 expression predicts poor prognosis. DAZAP1 may promote liver carcinoma cell proliferation, migration, and invasion of HEPG2 cells. CEUS parameters are related to the high DAZAP1 expression, and will help to differentiate the HCC tumor.
摘要:
目的:肝细胞癌(HCC)是最常见的肝癌类型之一。总体预后较差。DAZAP1,选择性剪接(AS)事件的调节剂,可能参与肿瘤生长。
方法:我们从齐齐哈尔医科大学附属第二医院肝外科收集了105例HCC患者和组织样本。使用R项目下载和操作TCGA数据集。通过定量RT-PCR和蛋白质印迹检测DAZAP1表达。CCK8实验用于研究细胞增殖,并采用transwell法检测体外迁移和侵袭能力。超声造影(CEUS)用于评估肿瘤的图像和参数。
结果:DAZAP1在HCC组织样本中高表达。肿瘤的峰强度(PI)和曲线下面积(AUC)高于肝实质,并与DAZAP1高表达相关。肿瘤CEUS参数与TNM分期相关,肿瘤大小,和血管。高DAZAP1表达与较短的生存时间和晚期组织学分级(G3-G4)相关。生物信息学分析表明,DAZAP1的下调鉴定出参与肿瘤生长过程的分化表达基因(DEG)。
结论:DAZAP1在肝癌中高表达,且与血流量有关。DAZAP1高表达预示预后不良。DAZAP1可能促进肝癌细胞增殖,迁移,和HEPG2细胞的侵袭。CEUS参数与高DAZAP1表达有关,并将有助于区分HCC肿瘤。
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