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

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

doi:10.3892/or.2017.5653

Cited by 27 publications

(27 citation statements)

References 37 publications

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“…Furthermore, in vitro investigations of PER2 overexpression in lung cancer LLC cells, breast cancer EMT6 cells, osteosarcoma MG63 cells, and pancreatic cancer Panc1 and Aspc1 cells have demonstrated significant increases in tumor cell apoptosis and marked decreases in cell proliferation (22)(23)(24). Our previous studies have also shown that knockdown of PER2 in OSCC cells can greatly enhance cell proliferation and reduce apoptosis (25,26). The aforementioned studies thus implicate PER2 as an important tumor-suppressor gene.…”

Section: Introductionmentioning

confidence: 86%

“…Our previous studies found that downregulating PER2 in OSCC cells could markedly reduce cell apoptosis (25,26). Caspase-8 is an important apoptosis-related gene, and its abnormal expression is closely associated with carcinogenesis (45).…”

Section: Per2 Expressionmentioning

confidence: 99%

“…Studies have revealed that PIK3CA and PTEN have an important role in the occurrence and development of OSCC (23)(24)(25)(26)(27)(28)(29)(30)(31). PIK3CA is the key molecule in the PI3K/AKT signaling pathway (40), while PTEN is the most important negative regulatory component in the PI3K/AKT signaling pathway (41).…”

Section: Per2 Expressionmentioning

confidence: 99%

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Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer

Xiong

Yang

et al. 2017

Int J Oncol

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Recent studies have demonstrated that abnormal expression of the clock gene PER2 is closely associated with the development of a variety of cancer types. However, the expression of PER2 in oral squamous cell carcinoma (OSCC), a common malignant tumor in humans, and its correlations with the clinicopathological parameters and survival time of OSCC patients and the altered expression of important tumor-related genes remain unclear. In the present study, we detected the mRNA and protein expression levels of PER2, PIK3CA, PTEN, P53, P14ARF and caspase‑8 in OSCC tissues and cancer-adjacent oral mucosa by reverse transcription-quantitative PCR (RT-qPCR), western blotting and immunohistochemistry. The results showed that the PER2, PTEN, P53, P14ARF and caspase‑8 mRNA and protein expression levels in OSCC were significantly reduced compared with those in cancer-adjacent tissues. Additionally, the PIK3CA protein expression level was significantly increased in OSCC tissues, whereas the mRNA level was not. Decreased expression of PER2 was signiﬁcantly associated with advanced clinical stage and the presence of lymphatic metastasis in OSCC patients. Patients with PER2‑negative expression had a significantly shorter survival time than those with PER2‑positive expression. PER2 expression was negatively correlated with PIK3CA and P53 levels, and positively correlated with PTEN, P14ARF and caspase‑8 levels. In summary, the results of this study suggest that loss of PER2 expression is closely associated with the genesis and development of OSCC and that PER2 may be an important prognostic biomarker in OSCC. PER2 may serve an antitumor role via the P53/P14ARF, PIK3CA/AKT and caspase‑8 pathways.

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Section: Introductionmentioning

confidence: 86%

Section: Per2 Expressionmentioning

confidence: 99%

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Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer

Xiong

Yang

et al. 2017

Int J Oncol

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“…Considering this underpinning role for Otolin‐1 , any circadian regulation of the organic matrix must occur through interaction with this crucial molecule. We found both MMP 2 and TIMP 2 , proteins whose expression likely follows a circadian pattern as knockout studies of the clock gene PER2 have resulted in a shift in their levels . MMP 2 catalyses the cleavage of several types of collagen, including type X.…”

Section: Discussionmentioning

confidence: 88%

The inner ear proteome of fish

et al. 2018

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The mechanisms that underpin the formation, growth and composition of otoliths, the biomineralized stones in the inner ear of fish, are largely unknown, as only a few fish inner ear proteins have been reported. Using a partial transcriptome for the inner ear of black bream (Acanthopagrus butcheri), in conjunction with proteomic data, we discovered hundreds of previously unknown proteins in the otolith. This allowed us to develop hypotheses to explain the mechanisms of inorganic material supply and daily formation of growth bands. We further identified a likely protein mediator of crystal nucleation and an explanation for the apparent metabolic inertness of the otolith. Due to the formation of both daily and annual increments, otoliths are routinely employed as natural chronometers, being used for age and growth estimation, fisheries stock assessments, and the reconstruction of habitat use, movement, diet and the impacts of climate change. Our findings provide an unprecedented view of otolith molecular machinery, aiding in the interpretation of these essential archived data.

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“…Finally, a new nomogram was generated combined risk score and clinicopathological characteristics. As displayed in the Figure 7A (31). With that in mind, disruption in timekeeping system could facilitate tumor progression(32), and circadian clock genes have also been reported to be involved in the carcinogenesis and prognosis of carcinomas (33), which may in turn contributes to the survival prognosis prediction and individualized medical treatment for patients.…”

Section: Patients Suffered From Unsatisfied Survival Time With Elevatmentioning

confidence: 99%

Genomics and Prognosis Analysis of Circadian clock genes in Hepatocellular Carcinoma

Guo

Lin

et al. 2020

Preprint

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Background: Circadian clock genes have been reported to exhibit a regulatory effect on the carcinogenesis and progression of numerous cancers. Nevertheless, the specific relationship between hepatocellular carcinoma (HCC) and circadian rhythm associated genes still remain to be clarified. Therefore, we evaluate the prognosis function of circadian clock genes in HCC with the online datasets of The Cancer Genome Atlas (TCGA) and the international cancer genome consortium (ICGC). Methods: In our research, the RNA-seq of the selected core circadian genes in HCC patients and their relevant clinical data were acquired from the online TCGA database and the ICGC database. R software and cBioPortal website were performed. Results: As consequence, among the 22 typical circadian clock genes, 16 genes were statistically expressed between HCC and adjacent normal tissues. Accordingly, 11 clock genes with regression coefficients were used to constitute a new risk score formula, which was related to the prognosis in HCC. Moreover, the new nomogram, which consisting risk score and several clinical traits , could be applied for the purpose of accurate prediction of the OS time for the patients. Finally, we identified a novel nomogram related with OS in HCC patients with a comprehensive analysis of circadian clock genes and other clinical characteristics profiles. It was also the first time we systematically demonstrated the relationship between clock genes and the HCC prognosis, which would contribute to the treatment of HCC. Conclusions: The current study demonstrated the potential of circadian clock genes as clinically associated biomarkers for prognosis prediction in HCC, which may make a significant contribution to the further investigations of HCC progression.

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

Cited by 27 publications

References 37 publications

Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer

Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer

The inner ear proteome of fish

Genomics and Prognosis Analysis of Circadian clock genes in Hepatocellular Carcinoma

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