Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, PR China.
Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, PR China; Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Gene. 2018 Oct 5;673:217-224. doi: 10.1016/j.gene.2018.06.028. Epub 2018 Jun 23.
Cervical cancer (CC) is one of the most common gynecologic tumors in women worldwide, with poor prognosis and low survival rate. In this study, we identified SNAP23 as a potential tumor suppressor gene in CC.
The expression of SNAP23 in tissues and cell lines were measured by qRT-PCR, western blot and IHC. Knockdown of SNAP23 by siRNA and ectopic expression of SNAP23 by overexpression plasmid were performed to observe the biological function of SNAP23 in CC. Xenograft nude mice models were established to measure its function in vivo.
SNAP23 was downregulated in CC tissues and had a negative correlation with advanced clinical characteristics. Ectopic expression of SNAP23 suppressed malignant phonotype of CC while knockdown of SNAP23 promoted the progression of CC in vitro. The flow cytometry analysis revealed that SNAP23 exerted its tumor suppressor activity via inducing G2/M cell cycle arrest. Moreover, xenograft tumor models showed that SNAP23 suppresses tumor growth in vivo.
Our results revealed that SNAP23 suppressed progression of CC and induced cell cycle G2/M arrest via upregulating p21 and downregulating CyclinB1.
宫颈癌（CC）是全球女性中最常见的妇科肿瘤之一，预后差，生存率低。本研究鉴定 SNAP23 为 CC 中的一个潜在肿瘤抑制基因。
通过 qRT-PCR、western blot 和 IHC 检测 SNAP23 在组织和细胞系中的表达。通过 siRNA 敲低 SNAP23 和过表达质粒过表达 SNAP23 来观察 SNAP23 在 CC 中的生物学功能。建立异种移植裸鼠模型来测量其体内功能。
SNAP23 在 CC 组织中下调，与晚期临床特征呈负相关。SNAP23 的异位表达抑制了 CC 的恶性表型，而 SNAP23 的敲低促进了 CC 的体外进展。流式细胞术分析显示，SNAP23 通过诱导 G2/M 细胞周期阻滞发挥其肿瘤抑制活性。此外，异种移植肿瘤模型表明 SNAP23 抑制体内肿瘤生长。
我们的结果表明，SNAP23 通过上调 p21 和下调 CyclinB1 抑制 CC 的进展并诱导细胞周期 G2/M 阻滞。
