囊泡过度表达的癌症生存促进蛋白 1 在肝癌增殖中的作用。

The role of vesicular overexpressed in cancer pro-survival protein 1 in hepatocellular carcinoma proliferation.

机构信息

Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China.

Department of Pathology, Enze Hospital, Wenzhou Medical University, Taizhou, Zhejiang, China.

出版信息

Cancer Biomark. 2020;28(1):9-20. doi: 10.3233/CBM-190574.

DOI:10.3233/CBM-190574

PMID:32083568

Abstract

BACKGROUND

Recently, hepatocellular carcinoma (HCC) has been ranked as the second leading cause of cancer-associated death. However, the underlying molecular mechanisms of HCC progression remain unclear. Vesicular overexpressed in cancer pro-survival protein 1 (VOPP1) could be upregulated in a quantity of human cancers, including squamous cell carcinoma (SCC), gastric cancer, and glioblastoma. However, the precise functional mechanism of VOPP1 in HCC remains poorly understood. The present study aimed to investigate the role of VOPP1 in HCC proliferation.

METHODS

Immunohistochemistry (IHC), Western blot and Reverse-transcription polymerase chain reaction (RT-PCR) were used to analyze the protein and mRNA expressions of VOPP1, mitogen-activated protein kinase (MAPK) 14, ribosomal protein S6 kinase β1 (RPS6KB1), cylindromatosis (CYLD) and Twist family bHLH transcription factor 1 (TWIST1). The cell proliferation and apoptosis were tested using Celigo cell imaging analyzer and annexin V-APC apoptosis detection kit respectively. Colony formation and tumor xenograft assays were performed to understand their roles in tumorigenicity.

RESULTS

The expression of VOPP1 in HCC samples was higher than that in adjacent noncancerous tissues by immunohistochemistry. In addition, the down-regulation of VOPP1 using shRNA inhibited cell proliferation and tumour growth, and induced cell apoptosis in vitro and in vivo. Furthermore, VOPP1 silencing increased the expression of MAPK14 and RPS6KB1, indicating that the MAPK and mTOR signalling pathways might be involved in VOPP1-mediated cancer cell proliferation.

CONCLUSION

The present data indicate that VOPP1 may play an important role in the progression of HCC by targeting the MAPK and mTOR signalling pathways, and that VOPP1 may potentially be a candidate as a novel molecular target for HCC therapy.

摘要

背景

肝细胞癌（HCC）已成为癌症相关死亡的第二大主要原因。然而，HCC 进展的潜在分子机制尚不清楚。在包括鳞状细胞癌（SCC）、胃癌和神经胶质瘤在内的多种人类癌症中，囊泡过表达的存活蛋白 1（VOPP1）可被上调。然而，VOPP1 在 HCC 中的精确功能机制仍知之甚少。本研究旨在探讨 VOPP1 在 HCC 增殖中的作用。

方法

采用免疫组织化学（IHC）、Western blot 和逆转录聚合酶链反应（RT-PCR）分析 VOPP1、丝裂原活化蛋白激酶（MAPK）14、核糖体蛋白 S6 激酶β1（RPS6KB1）、圆柱瘤（CYLD）和 TWIST 家族 bHLH 转录因子 1（TWIST1）的蛋白和 mRNA 表达。使用 Celigo 细胞成像分析仪和膜联蛋白 V-APC 凋亡检测试剂盒分别检测细胞增殖和凋亡。进行集落形成和肿瘤异种移植实验以了解它们在致瘤性中的作用。

结果

IHC 结果显示，VOPP1 在 HCC 样本中的表达高于相邻非癌组织。此外，使用 shRNA 下调 VOPP1 可抑制细胞增殖和肿瘤生长，并在体外和体内诱导细胞凋亡。此外，VOPP1 沉默增加了 MAPK14 和 RPS6KB1 的表达，表明 MAPK 和 mTOR 信号通路可能参与了 VOPP1 介导的癌细胞增殖。