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BCAT1促进肝细胞癌中肿瘤细胞的迁移和侵袭。

BCAT1 promotes tumor cell migration and invasion in hepatocellular carcinoma.

作者信息

Xu Meng, Liu Qingquan, Jia Yuli, Tu Kangsheng, Yao Yingmin, Liu Qingguang, Guo Cheng

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

出版信息

Oncol Lett. 2016 Oct;12(4):2648-2656. doi: 10.3892/ol.2016.4969. Epub 2016 Aug 8.

Abstract

Branched-chain amino acid transaminase 1 (BCAT1) has been associated with numerous types of tumors; however, few previous studies have evaluated the expression and role of BCAT1 in hepatocellular carcinoma (HCC). In the present study, the expression of BCAT1 was detected by reverse transcription-quantitative polymerase chain reaction and immunoblotting in six HCC cell lines and 74 pairs of HCC and adjacent non-cancerous liver tissues. In addition, the correlation between the expression levels of c-Myc and BCAT1 was analyzed using immunohistochemistry. Furthermore, RNA silencing was performed using c-Myc-specific or BCAT1-specific small interfering RNA, after which wound healing and Transwell cell invasion assays were performed. Finally, the clinicopathological characteristics of BCAT1 in patients with HCC were analyzed. It was shown that the expression of BCAT1 was significantly higher in HCC tissues compared with adjacent non-tumor tissues (P<0.001), and in HCC cell lines compared within the L-02 hepatic cell line (P<0.001). In addition, immunohistochemical analyses indicated that the expression of BCAT1 was positively correlated with c-Myc (r=0.706, P<0.001). BCAT1 expression was shown to be downregulated in c-Myc-knockdown cells, and silencing of BCAT1 expression reduced the invasion and migration of HCC cells. Furthermore, a clinical analysis indicated that BCAT1 expression in HCC tissues was significantly associated with the tumor-node-metastasis stage, tumor number and tumor differentiation (all P<0.05), and that BCAT1 was able to predict the 5-year survival and disease-free survival rates of patients with HCC (both P<0.001). The results of the present study suggested that BCAT1 expression is upregulated in patients with HCC, and that BCAT1 may serve as a potential molecular target for the diagnosis and treatment of HCC.

摘要

支链氨基酸转氨酶1(BCAT1)与多种类型的肿瘤相关;然而,先前很少有研究评估BCAT1在肝细胞癌(HCC)中的表达及作用。在本研究中,通过逆转录定量聚合酶链反应和免疫印迹法检测了6种HCC细胞系以及74对HCC组织和癌旁非癌肝组织中BCAT1的表达。此外,采用免疫组织化学分析了c-Myc与BCAT1表达水平之间的相关性。进一步地,使用c-Myc特异性或BCAT1特异性小干扰RNA进行RNA沉默,之后进行伤口愈合和Transwell细胞侵袭实验。最后,分析了HCC患者中BCAT1的临床病理特征。结果显示,与癌旁非肿瘤组织相比,BCAT1在HCC组织中的表达显著更高(P<0.001),与L-02肝细胞系相比,在HCC细胞系中的表达也显著更高(P<0.001)。此外,免疫组织化学分析表明,BCAT1的表达与c-Myc呈正相关(r=0.706,P<0.001)。在c-Myc敲低的细胞中,BCAT1表达下调,并且BCAT1表达的沉默降低了HCC细胞的侵袭和迁移能力。此外,临床分析表明,HCC组织中BCAT1的表达与肿瘤-淋巴结-转移分期、肿瘤数量和肿瘤分化显著相关(均P<0.05),并且BCAT1能够预测HCC患者的5年生存率和无病生存率(均P<0.001)。本研究结果表明,HCC患者中BCAT1表达上调,并且BCAT1可能作为HCC诊断和治疗的潜在分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a72/5038498/a6b697c29d51/ol-12-04-2648-g00.jpg

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