Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; Department of Gastroenterology, Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
EBioMedicine. 2019 Oct;48:100-116. doi: 10.1016/j.ebiom.2019.09.007. Epub 2019 Oct 6.
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.
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.
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.
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).
SWELL1 最近被证明是容积调节阴离子通道 (VRAC) 的不可或缺的一部分。VRAC 据报道参与细胞增殖、存活和迁移。然而，SWELL1 与肝细胞癌 (HCC) 之间的关系仍知之甚少。在这项研究中，我们试图探讨 SWELL1 在 HCC 中的作用。
使用免疫组织化学和定量实时 PCR (qRT-PCR) 测量来自 HCC 患者的 HCC 样本中 SWELL1 的表达。通过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、Annexin V 和 PI 染色、划痕愈合、Transwell 等在内的相应细胞学实验分析 SWELL1 对 HCC 细胞增殖、凋亡和转移的影响。使用 BALB/c 裸鼠进行体内测定。进行 qRT-PCR 和 Western blot 以研究分子机制。
SWELL1 在 HCC 组织中高表达，并与不良预后相关。在体外，SWELL1 的过表达显著诱导细胞增殖和迁移，并抑制凋亡，而抑制 SWELL1 则产生相反的效果。此外，SWELL1 的敲低抑制了 HCC 体内的生长和转移。进一步的实验表明，SWELL1 通过与 PKCa 在信号水平上的连接激活 cyclinD1/CDK2 途径诱导细胞生长，并通过 JNK 途径调节 HCC 中的细胞迁移。
SWELL1 作为 HCC 细胞生长和转移的促进因子，可能是 HCC 的潜在干预靶点。
本工作得到国家自然科学基金（No. 81572422, 81700515）的支持。
