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凝溶胶蛋白样肌动蛋白封端蛋白(CapG)在人肝细胞癌细胞质中过表达,与细胞侵袭、迁移及肿瘤预后相关。

Gelsolin-like Actin-capping Protein (CapG) Overexpression in the Cytoplasm of Human Hepatocellular Carcinoma, Associated with Cellular Invasion, Migration and Tumor Prognosis.

作者信息

Tsai Tsung-Jung, Chao Wen-Ying, Chen Chien-Chin, Chen Yi-Ju, Lin Ching-Yen, Lee Ying-Ray

机构信息

Department of Gastroenterology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan, R.O.C.

Department of Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan, R.O.C.

出版信息

Anticancer Res. 2018 Jul;38(7):3943-3950. doi: 10.21873/anticanres.12680.

Abstract

BACKGROUND/AIM: Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Patients with metastatic HCC (mHCC) show poor prognosis and high mortality. In previous reports, gelsolin-like actin-capping protein (CapG) has been demonstrated to regulate cancer invasion and metastasis in various human cancers. In this study, the expression of CapG was verified in normal and/or HCCs' specimens and HCC cell lines. Moreover, the bio-activity of CapG was also investigated.

MATERIALS AND METHODS

The expression of CapG was examined in HCC's tissue-array by immunohistochemical (IHC) staining. The mRNA and protein of CapG in three HCC cell lines were determined using real-time RT-PCR and western blot. Moreover, a trans-well migration model and a matrigel-trans-well invasion assay were used to address the bio-activity of CapG in HCC cell lines.

RESULTS

CapG was detected in the cytoplasm of normal liver tissue and HCC specimens. Importantly, CapG expression was elevated in the HCC specimens compared to normal cases and was significantly overexpressed in mHCC cases compared to normal cases. Moreover, patients with highly expressed CapG showed greater mortality in HCC cases. In addition, the RNA and protein levels of CapG among three HCC cell lines showed a positive association with cellular migration and invasive ability. CapG knockdown with shRNA in HCC cells also verified this finding.

CONCLUSION

In the present study, it is demonstrated that CapG is expressed in the cytoplasm and could be used as a prognostic or diagnostic biomarker for mHCC in clinical specimens. Moreover, CapG might contribute to tumor motility and cancer-associated mortality.

摘要

背景/目的:人类肝细胞癌(HCC)是全球最常见的癌症之一。转移性肝细胞癌(mHCC)患者预后较差且死亡率高。在以往的报道中,凝溶胶蛋白样肌动蛋白封端蛋白(CapG)已被证明可调节多种人类癌症中的癌症侵袭和转移。在本研究中,验证了CapG在正常和/或肝癌标本以及肝癌细胞系中的表达。此外,还研究了CapG的生物活性。

材料与方法

通过免疫组织化学(IHC)染色检测CapG在肝癌组织芯片中的表达。使用实时RT-PCR和蛋白质印迹法测定三种肝癌细胞系中CapG的mRNA和蛋白质。此外,采用Transwell迁移模型和基质胶Transwell侵袭试验来研究CapG在肝癌细胞系中的生物活性。

结果

在正常肝组织和肝癌标本的细胞质中检测到CapG。重要的是,与正常病例相比,CapG在肝癌标本中的表达升高,与正常病例相比,在mHCC病例中显著过表达。此外,CapG高表达的患者在肝癌病例中的死亡率更高。此外,三种肝癌细胞系中CapG的RNA和蛋白质水平与细胞迁移和侵袭能力呈正相关。在肝癌细胞中用shRNA敲低CapG也证实了这一发现。

结论

在本研究中,证明CapG在细胞质中表达,可作为临床标本中mHCC的预后或诊断生物标志物。此外,CapG可能有助于肿瘤的运动性和癌症相关死亡率。

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