| Title |
The important tumor suppressor role of PER1 in regulating the cyclin–CDK–CKI network in SCC15 human oral squamous cell carcinoma cells
|
|---|---|
| Published in |
OncoTargets and therapy, April 2016
|
| DOI | 10.2147/ott.s100952 |
| Pubmed ID | |
| Authors |
Xiao-Juan Fu, Han-Xue Li, Kai Yang, Dan Chen, Hong Tang |
| Abstract |
Accumulating evidence suggests that the abnormal expression of the circadian clock gene PER1 is closely related to the development and progression of cancer. However, the exact molecular mechanism by which the abnormal expression of PER1 induces carcinogenesis is unclear. This study was conducted to investigate the alterations in downstream cell cycle genes, cell cycle distribution, cell proliferation, apoptosis, and in vivo tumorigenicity in SCC15 oral squamous cell carcinoma cells after PER1 downregulation. A stable SCC15 cell line was established to constitutively express shRNA targeting PER1. Quantitative real-time polymerase chain reaction (PCR) and Western blot analyses were conducted to estimate PER1 mRNA and protein expression. The expression of PER1, P53, CyclinD1, CyclinE, CyclinA2, CyclinB1, cyclin-dependent kinase (CDK) 1, CDK2, CDK4, CDK6, P16, P21, WEE1, and CDC25 mRNA was detected by quantitative real-time PCR. Cell cycle distribution, cell proliferation, and apoptosis were determined by flow cytometry. The in vivo tumorigenicity of SCC15 cells was evaluated in female BALB/c nu/nu mice. PER1 downregulation resulted in significantly increased mRNA expression levels of CyclinD1, CyclinE, CyclinB1, CDK1, and WEE1 (P<0.05), and significantly decreased mRNA expression levels of P53, CyclinA2, P16, P21, and CDC25 (P<0.05) compared to control cells. Additionally, PER1 downregulation led to significantly fewer cells in S phase (P<0.05), but significantly more cells in G2/M phase (P<0.05) compared to the control group. After PER1 downregulation, the cell proliferation index was significantly higher (P<0.05), and the apoptotic index was significantly lower (P<0.05). The in vivo tumorigenicity of SCC15 cells was significantly enhanced by PER1 downregulation (P<0.05). PER1 is an important tumor suppressor gene which acts by regulating the Cyclin-CDK-cyclin-dependent kinase inhibitor regulatory network. An in-depth characterization of this gene may further illuminate the molecular mechanisms responsible for the development and progression of cancer, thus providing novel molecular targets for cancer treatment. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Sweden | 1 | 2% |
| Unknown | 44 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 10 | 22% |
| Student > Ph. D. Student | 7 | 16% |
| Student > Bachelor | 6 | 13% |
| Student > Doctoral Student | 3 | 7% |
| Professor | 3 | 7% |
| Other | 6 | 13% |
| Unknown | 10 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 14 | 31% |
| Medicine and Dentistry | 10 | 22% |
| Agricultural and Biological Sciences | 2 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
| Unspecified | 1 | 2% |
| Other | 4 | 9% |
| Unknown | 13 | 29% |
Attention Score in Context
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#22,756,649
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Outputs from OncoTargets and therapy
#2,078
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Outputs of similar age from OncoTargets and therapy
#86
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