TSPAN12 通过细胞周期控制在前卵巢癌肿瘤增殖中发挥作用。

TSPAN12 Precedes Tumor Proliferation by Cell Cycle Control in Ovarian Cancer.

机构信息

Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.

Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, Harbin, China.

出版信息

Mol Cells. 2019 Jul 31;42(7):557-567. doi: 10.14348/molcells.2019.0015.

DOI:10.14348/molcells.2019.0015

PMID:31362470

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6681867/

Abstract

TSPAN12, a member of the tetraspanin family, has been highly connected with the pathogenesis of cancer. Its biological function, however, especially in ovarian cancer (OC), has not been well elucidated. In this study, The Cancer Genome Atlas (TCGA) dataset analysis revealed that upregulation of gene expression was significantly correlated with patient survival, suggesting that TSPAN12 might be a potential prognostic marker for OC. Further exploration showed that TSPAN12 overexpression accelerated proliferation and colony formation of OVCAR3 and SKOV3 OC cells. Knockdown of TSPAN12 expression in A2780 and SKOV3 cells decreased both proliferation and colony formation. Western blot analysis showed that several cyclins and cyclin-dependent kinases (CDK) (e.g., Cyclin A2, Cyclin D1, Cyclin E2, CDK2, and CDK4) were significantly involved in the regulation of cell cycle downstream of TSPAN12. Moreover, TSPAN12 accelerated mitotic progression by controlling cell cycle. Thus, our data demonstrated that TSPAN12 could be a novel molecular target for the treatment of OC.

摘要

TSPAN12 是四跨膜蛋白家族的成员，与癌症的发病机制高度相关。然而，其生物学功能，特别是在卵巢癌（OC）中的作用，尚未得到充分阐明。在这项研究中，癌症基因组图谱（TCGA）数据集分析显示，基因表达上调与患者生存显著相关，提示 TSPAN12 可能是 OC 的潜在预后标志物。进一步探索表明，TSPAN12 过表达可加速 OVCAR3 和 SKOV3 OC 细胞的增殖和集落形成。在 A2780 和 SKOV3 细胞中敲低 TSPAN12 表达会降低细胞增殖和集落形成。Western blot 分析表明，几种细胞周期蛋白和细胞周期蛋白依赖性激酶（CDK）（例如细胞周期蛋白 A2、细胞周期蛋白 D1、细胞周期蛋白 E2、CDK2 和 CDK4）在下调 TSPAN12 后显著参与细胞周期的调节。此外，TSPAN12 通过控制细胞周期加速有丝分裂进程。因此，我们的数据表明 TSPAN12 可能是治疗 OC 的新的分子靶点。