Oncotarget

Research Papers:

The clock gene PER1 plays an important role in regulating the clock gene network in human oral squamous cell carcinoma cells

Qin Zhao, Gang Zheng, Kai Yang _, Yi-ran Ao, Xiao-li Su, Yu Li and Xiao-qiang Lv

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Oncotarget. 2016; 7:70290-70302. https://doi.org/10.18632/oncotarget.11844

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Abstract

Qin Zhao1, Gang Zheng2, Kai Yang1, Yi-ran Ao1, Xiao-li Su1, Yu Li3, Xiao-qiang Lv1

1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing 400016, China

2Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China

3Department of Pathology, Chongqing Medical University, Chongqing 400016, China

Correspondence to:

Kai Yang, email: cqfyyk@hotmail.com

Keywords: circadian clock, oral cancer, PER1, gene

Received: June 20, 2016    Accepted: August 26, 2016    Published: September 02, 2016

ABSTRACT

The various clock genes in normal cells, through their interaction, establish a number of positive and negative feedback loops that compose a network structure. These genes play an important role in regulating normal physiological activities. The expression of clock gene PER1 is decreased in many types of cancer. PER1 is highly correlated with the initiation and progression of cancer by regulating numerous downstream genes. However, it is still unclear whether the lower expression of PER1 in cancer can influence the expression of other clock genes in the clock gene network. In this study, we used short hairpin RNA interference to knock down PER1 effectively in SCC15 human oral squamous cell carcinoma cells. These cancer cells later were subcutaneously injected into the back of nude mice. We discovered that after PER1 knockdown, apoptosis was decreased and cell proliferation and in vivo tumor formation were enhanced. Quantitative real-time PCR result indicated that in vitro and in vivo cancer cells after PER1 knockdown, PER2, DEC1, DEC2, CRY1, CRY2 and NPAS2 were significantly down-regulated at the mRNA level, while PER3, TIM, RORα and REV-ERBα were significantly up-regulated. It prompts that the role of PER1 in carcinogenesis is exerted not only by regulating downstream genes, but also through the synergistic dysregulation of many other clock genes in the clock gene network.


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