Circadian clock gene Per2 downregulation in non‑small cell lung cancer is associated with tumour progression and metastasis

Xiang, Run; Cui, Yue; Wang, Yanping; Xie, Ting; Yang, Xiao‐Jun; Wang, Zhu; Li, Juan; Li, Qiang

doi:10.3892/or.2018.6704

Cited by 41 publications

(34 citation statements)

References 29 publications

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“…To explore the role of the classical circadian gene PER2 in OSCC, we performed this study and revealed that PER2 expression and nucleus-translocation were both downregulated in OSCC tissues and cells as well as ANT. Similar to the results in non-small-cell lung cancer [20], PER2 overexpression significantly inhibited the proliferation, migration, and invasion of OSCC cells, indicating that PER2 might act as a crucial antitumor gene. e growth of in vivo tumors was also suppressed resulting from the upregulation of PER2 in derived OSCC cells.…”

Section: Discussionsupporting

confidence: 83%

Aberrant Expression and Subcellular Localization of PER2 Promote the Progression of Oral Squamous Cell Carcinoma

Guo

Tang

Chen

et al. 2020

BioMed Research International

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Oral squamous cell carcinoma, one of the most prevalent cancer types in the world, has been confirmed under the influence of a key circadian gene, PER2, whose role has been identified in the development of some other types of cancers. However, the mechanism through which PER2 regulates the progress of OSCC remains largely unknown. In this study, we showed that besides the abnormal expression and subcellular localization of PER2 observed in OSCC tissues and cells as expected, these anomalous changes also existed in the adjacent noncancerous tissues, which was a novel finding in our research. The phase of PER2 rhythmic expression pattern in OSCC cells was later than that in oral keratinocytes in the protein level. In addition, we demonstrated that PER2 played as a resistant factor in the development of OSCC by upregulating TP53 and inhibiting epithelial-mesenchymal transition in vitro and in vivo. Taken together, our results identified that the development of OSCC is closely associated with PER2, the aberrant expression and subcellular localization of which facilitates the malignant progress.

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Section: Discussionsupporting

confidence: 83%

Aberrant Expression and Subcellular Localization of PER2 Promote the Progression of Oral Squamous Cell Carcinoma

Guo

Tang

Chen

et al. 2020

BioMed Research International

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“…A few studies have exemplified that the expression of the circadian clock gene Per2 is markedly downregulated in non-small cell lung cancer, breast cancer, ovarian cancer, gastric cancer, colorectal cancer and liver cancer [17-19, 22, 23], and it is tightly connected to the occurrence and development of cancer. Xiang et al reported that overexpression of Per2 distinctly inhibits tumor cell growth, migration and invasion [12,19,24]. Previous studies have also reported that overexpression of Per2 promotes apoptosis and inhibits proliferation in glioma, breast, leukemia and lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of the clock gene Per2 suppresses oral squamous cell carcinoma progression by activating autophagy via the PI3K/AKT/mTOR pathway

Liu¹,

Gong²,

Yang³

2020

J. Cancer

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The current studies reveal that the clock gene Per2 is expressed at lower levels in a variety of tumors and plays a significant tumor suppressor role. However, the biological functions and mechanism of Per2 in OSCC (OSCC: oral squamous cell carcinoma) remain unclear. In this study, OSCC cells with stable overexpression or silencing of Per2 were established to explore their biological functions and mechanism in vivo and in vitro. We discovered that the expression of Per2 decreases in OSCC cells. Overexpression of Per2 promoted autophagy and apoptosis in OSCC cells and inhibited proliferation. The opposite results were obtained in Per2-silenced OSCC cells. In Per2-overexpressing OSCC cells, the expression levels of PIK3CA, p-AKT, p-mTOR, p62 and Beclin1 were significantly reduced and the LC3B II/I ratio was significantly increased. In contrast, in Per2-silenced OSCC cells, the expression levels of PIK3CA, p-AKT, p-mTOR, p62 and Beclin1 were significantly enhanced and the LC3B II/I ratio was significantly reduced. When the AKT activator SC79 was added to Per2-overexpressing OSCC cells, the increased autophagy, apoptosis and decreased proliferation were significantly rescued. Furthermore, when autophinib, an autophagy inhibitor, was added to Per2-overexpressing OSCC cells, the decreased proliferation and increased apoptosis were significantly restored. An in vivo tumorigenesis assay also confirmed that overexpression of Per2 suppresses the growth of OSCC. In conclusion, our research results demonstrate that Per2 suppresses OSCC progression by motivating autophagy, as well as inhibiting cell proliferation and promoting apoptosis, which were mediated by autophagy, in a PI3K/AKT/mTOR pathway-dependent manner. Per2 could potentially be used as a valuable therapeutic marker for OSCC.

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“…The proteins encoding by PER2, GADD45A, and TPD52 genes are also involved in the cancer cell proliferation and tumor growth and are dysregulated in cancer cells (Wang et al 2016;Xiang et al 2018;Xiong et al 2018;Zhang et al 2018;Hu et al 2019;Rahman et al 2019). At the same time, the expression of these genes was resistant to the silencing of adipokine NAMPT in the glioma cells.…”

Section: Discussionmentioning

confidence: 99%

Silencing of NAMPT leads to up-regulation of insulin receptor substrate 1 gene expression in U87 glioma cells

Tsymbal

Minchenko

Luzina

et al. 2020

Endocrine Regulations

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Objective. The aim of the present study was to investigate the effect of adipokine NAMPT (nicotinamide phosphoribosyltransferase) silencing on the expression of genes encoding IRS1 (insulin receptor substrate 1) and some other proliferation related proteins in U87 glioma cells for evaluation of the possible significance of this adipokine in intergenic interactions.Methods. The silencing of NAMPT mRNA was introduced by NAMPT specific siRNA. The expression level of NAMPT, IGFBP3, IRS1, HK2, PER2, CLU, BNIP3, TPD52, GADD45A, and MKI67 genes was studied in U87 glioma cells by quantitative polymerase chain reaction. Anti-visfatin antibody was used for detection of NAMPT protein by Western-blot analysis.Results. It was shown that the silencing of NAMPT mRNA led to a strong down-regulation of NAMPT protein and significant modification of the expression of IRS1, IGFBP3, CLU, HK2, BNIP3, and MKI67 genes in glioma cells and a strong up-regulation of IGFBP3 and IRS1 and down-regulation of CLU, BNIP3, HK2, and MKI67 gene expressions. At the same time, no significant changes were detected in the expression of GADD45A, PER2, and TPD52 genes in glioma cells treated by siRNA specific to NAMPT. Furthermore, the silencing of NAMPT mRNA suppressed the glioma cell proliferation.Conclusions. Results of this investigation demonstrated that silencing of NAMPT mRNA with corresponding down-regulation of NAMPT protein and suppression of the glioma cell proliferation affected the expression of IRS1 gene as well as many other genes encoding the proliferation related proteins. It is possible that dysregulation of most of the studied genes in glioma cells after silencing of NAMPT is reflected by a complex of intergenic interactions and that NAMPT is an important factor for genome stability and regulatory mechanisms contributing to the control of glioma cell metabolism and proliferation.

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Circadian clock gene Per2 downregulation in non‑small cell lung cancer is associated with tumour progression and metastasis

Cited by 41 publications

References 29 publications

Aberrant Expression and Subcellular Localization of PER2 Promote the Progression of Oral Squamous Cell Carcinoma

Aberrant Expression and Subcellular Localization of PER2 Promote the Progression of Oral Squamous Cell Carcinoma

Overexpression of the clock gene Per2 suppresses oral squamous cell carcinoma progression by activating autophagy via the PI3K/AKT/mTOR pathway

Silencing of NAMPT leads to up-regulation of insulin receptor substrate 1 gene expression in U87 glioma cells

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