中国医学科学院学报

高级检索
中国医学科学院学报

中国医学科学院学报 ›› 2016, Vol. 38 ›› Issue (2): 155-163.doi: 10.3881/j.issn.1000-503X.2016.02.006

• 论著 • 上一篇    下一篇

生物钟基因Per1对人口腔鳞癌细胞生物学行为的影响和调控机制

李晗雪, 杨凯(), 付小娟, 赵钦   

  1. 重庆医科大学 附属第一医院口腔颌面外科,重庆 400016
  • 收稿日期:2015-11-02 出版日期:2016-02-15 发布日期:2016-04-10
  • 作者简介:

    通信作者:杨 凯 电话:023-89012907,电子邮件:cqfyyk@aliyun.com

Effect and Regulatory Mechanism of Clock Gene Per1 on Biological Behaviors of Human Oral Squamous Carcinoma Cell

Han-xue LI, Kai YANG(), Xiao-juan FU, Qin ZHAO   

  1. Department of Oral and Maxillofacial Surgery,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China
  • Received:2015-11-02 Online:2016-02-15 Published:2016-04-10

摘要:

目的 探讨生物钟基因Per1对人口腔鳞癌细胞SCC15增殖、凋亡、迁移和侵袭的影响及调控机制。方法 采用RNA干扰技术沉默SCC15细胞内Per1基因,应用流式细胞仪检测沉默后细胞的增殖和凋亡水平,Transwell小室检测细胞迁移和侵袭能力的改变,实时荧光定量PCR检测Ki-67、鼠双微基因2(MDM2)、c-Myc、p53、Bax、Bcl-2、金属蛋白酶(MMP)2、MMP9和血管内皮生长因子(VEGF)mRNA的表达情况。结果 沉默SCC15癌细胞内Per1基因后促进了细胞的增殖,抑制了细胞凋亡,增强了细胞的迁移和侵袭能力 (P均<0.05)。Per1基因的低表达显著提高了Ki-67、MDM2、Bcl-2、MMP2 和MMP9 mRNA的表达(P均<0.05),降低了c-Myc、p53和Bax mRNA的表达(P均<0.05),而VEGF mRNA的表达差异无统计学意义(P>0.05)。结论 生物钟基因Perl能调控下游重要的肿瘤相关基因Ki-67、MDM2、c-Myc、p53、Bax、Bcl-2、MMP2和MMP9,其表达变化影响癌细胞的增殖、凋亡、迁移和侵袭,对Per1深入研究有可能进一步明确癌症的发生发展机制,为癌症的治疗提供新的有效分子靶点。

关键词: 生物钟基因, Per1, 口腔, 癌, 鳞状细胞

Abstract:

Objective To investigate the effect and regulatory mechanism of clock gene Per1 on the proliferation,apoptosis,migration,and invasion of human oral squamous carcinoma SCC15 cells. Methods RNA interference was used to knock down Per1 gene in human oral squamous cell carcinoma SCC15 cell line. Changes of cell proliferation and apoptosis were analyzed by flow cytometry. Transwell assay was carried out to assess cell migration and invasion. Real-time polymerase chain reaction was used to detect the mRNA expressions of Ki-67,murine double minute 2(MDM2),c-Myc,p53,Bax,Bcl-2,metalloproteinase (MMP)2,MMP9,and vascular endothelial growth factor (VEGF). Results shRNA-mediated knockdown of Per1 promoted the proliferation,migration and invasion capacity,and inhibited cell apoptosis capacity of SCC15 cells (all P<0.05). Additionally,Per1 knockdown also increased the mRNA expressions of Ki-67,MDM2,Bcl-2,MMP2,and MMP9 and decreased the mRNA expressions of c-Myc,p53,and Bax (all P<0.05);however,the VEGF mRNA expression did not differ significantly after Per1 knockdown (P>0.05). Conclusions Clock gene Perl can regulate important tumor-related genes downstream such as Ki-67,MDM2,c-Myc,p53,Bax,Bcl-2,MMP2,and MMP9,and the aberrant expression of Per1 can affect tumor cell proliferation,apoptosis,migration and invasion. An in-depth study of Per1 may further clarify the mechanism of tumorigenesis and tumor development and thus provides new effective molecular targets for cancer treatment.

Key words: clock gene, Per1, oral cavity, carcinoma, squamous cell

中图分类号: