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昼夜节律时钟基因PER2通过调控人类口腔鳞状细胞癌中的肿瘤相关基因在肿瘤抑制中发挥重要作用。

The circadian clock gene PER2 plays an important role in tumor suppression through regulating tumor-associated genes in human oral squamous cell carcinoma.

作者信息

Su Xiaoli, Chen Dan, Yang Kai, Zhao Qin, Zhao Dan, Lv Xiaoqiang, Ao Yiran

机构信息

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China.

出版信息

Oncol Rep. 2017 Jul;38(1):472-480. doi: 10.3892/or.2017.5653. Epub 2017 May 19.

Abstract

Low expression of the clock gene PER2 is closely related to carcinogenesis and the development of cancer; however, the mechanism of the low expression of PER2 that led to cell malignant transformation remains unclear. This study used RNA interference (RNAi) technology to silence PER2 in SCC15 human oral squamous cell carcinoma (OSCC) cells. Then it was found that the ability of cancer cell proliferation, migration, and invasion were markedly increased (P<0.05), and the ability of cancer cell apoptosis and the number of cells in G1/G0 phase were markedly reduced (P<0.05) after PER2 knockdown. PER2 knockdown increased the expression of Ki-67, MDM2, c-Myc, Bcl-2, MMP2, and VEGF mRNA (P<0.05), and decreased the expression of p53, Bax, and TIMP-2 mRNA (P<0.05). The in vivo experiments also proved that the tumorigenicity of SCC15 cells was significantly enhanced after PER2 silence (P<0.05). Overall, these results show that PER2 through the regulation of the numerous important downstream tumor-related genes, plays a major role in tumor suppression, and it may be a novel molecular target for cancer treatment.

摘要

生物钟基因PER2的低表达与肿瘤发生及癌症发展密切相关;然而,导致细胞恶性转化的PER2低表达机制仍不清楚。本研究利用RNA干扰(RNAi)技术使人类口腔鳞状细胞癌(OSCC)SCC15细胞中的PER2基因沉默。结果发现,PER2基因敲低后,癌细胞的增殖、迁移及侵袭能力显著增强(P<0.05),而癌细胞凋亡能力及G1/G0期细胞数量显著减少(P<0.05)。PER2基因敲低使Ki-67、MDM2、c-Myc、Bcl-2、MMP2及VEGF mRNA的表达增加(P<0.05),使p53、Bax及TIMP-2 mRNA的表达降低(P<0.05)。体内实验也证明,PER2沉默后SCC15细胞的致瘤性显著增强(P<0.05)。总体而言,这些结果表明,PER2通过调控众多重要的下游肿瘤相关基因,在肿瘤抑制中发挥主要作用,可能是癌症治疗的一个新分子靶点。

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