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首页> 外文期刊>EBioMedicine >SWELL1 promotes cell growth and metastasis of hepatocellular carcinoma in vitro and in vivo
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SWELL1 promotes cell growth and metastasis of hepatocellular carcinoma in vitro and in vivo

机译：SWELL1在体内和体外促进肝细胞癌的细胞生长和转移

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Background SWELL1 was recently demonstrated to be an indispensable part of the volume-regulated anion channel (VRAC). VRAC is reported to participate in cell proliferation, survival, and migration. However, the correlation between SWELL1 and hepatocellular carcinoma (HCC) remains poorly-understood. In this study, we tried to explore the role of SWELL1 in HCC. Methods Immunohistochemistry and quantitative real-time-PCR (qRT-PCR) was used to measure SWELL1 expression in HCC samples obtained from patients with HCC. The effects of SWELL1 on HCC cell proliferation, apoptosis, and metastasis were analysed by corresponding cytological experiments including Cell Counting Kit-8 (CCK8), colony-forming, 5-ethynyl-2′-deoxyuridine (EdU), cell cycle analysis, TUNEL, Annexin V and PI staining, wound healing, transwell, and so on. BALB/c nude mice were used for the in vivo assays. qRT-PCR and western blotting was performed for molecular mechanisms. Findings SWELL1 was highly expressed in HCC tissues, and related to the poor prognosis. In vitro, the over-expression of SWELL1 significantly induced cell proliferation and migration, and inhibited apoptosis, whereas suppressing SWELL1 had the opposite effects. Moreover, knockdown of SWELL1 suppressed the growth and metastasis of HCC in vivo. Further experiments revealed that SWELL1 induced cell growth by activating the cyclinD1/CDK2 pathway via the connection with PKCa at the signalling level, and regulated cell migration through the JNK pathway in HCC. Interpretation SWELL1 acts as a promoter in the growth and metastasis of HCC cells and may be a potential intervention target for HCC. Fund This work is supported by the National Natural Science Foundation of China (No. 81572422 , 81700515 ).
机译：背景技术最近，SWELL1被证明是体积调节阴离子通道（VRAC）不可或缺的一部分。据报道，VRAC参与细胞增殖，存活和迁移。但是，SWELL1与肝细胞癌（HCC）之间的相关性仍知之甚少。在这项研究中，我们试图探索SWELL1在肝癌中的作用。方法采用免疫组织化学和实时荧光定量PCR（qRT-PCR）方法检测肝癌患者肝癌组织中SWELL1的表达。通过相应的细胞学实验分析了SWELL1对HCC细胞增殖，凋亡和转移的影响，包括细胞计数试剂盒8（CCK8），集落形成，5-乙炔基2'-脱氧尿苷（EdU），细胞周期分析，TUNEL ，膜联蛋白V和PI染色，伤口愈合，transwell等。 BALB / c裸鼠用于体内测定。进行了qRT-PCR和蛋白质印迹的分子机制。结果SWELL1在肝癌组织中高表达，与预后不良有关。在体外，SWELL1的过表达显着诱导细胞增殖和迁移，并抑制细胞凋亡，而抑制SWELL1具有相反的作用。此外，敲除SWELL1抑制体内HCC的生长和转移。进一步的实验表明，SWELL1通过在信号水平上通过与PKCa的连接激活cyclinD1 / CDK2途径来诱导细胞生长，并通过HCC中的JNK途径调节细胞迁移。解释SWELL1在HCC细胞的生长和转移中起启动子的作用，并且可能是HCC的潜在干预目标。基金这项工作得到了国家自然科学基金的资助（第81572422号，第81700515号）。

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