Abstract
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.
Highlights
Oral squamous cell carcinoma (OSCC) is one of the most common tumors in head and neck malignancies with high cancer-related mortality rates worldwide [1]
The circadian clock plays a pivotal role in orchestrating physiological, biochemical, and behavior processes to better adapt to the diurnal stimulus in the environment [6, 7]. e current molecular model of circadian clock is a classical key feedback loop, where the heterodimer of CLOCK and BMAL1 determines the rhythmic expression of genes containing E-box elements such as PERs and CRYs, which in turn form negative regulating complexes that interact with CLOCK-BMAL1 [6, 8, 9]
We found that there were significant differences between the expression and subcellular localization of PER2 in OSCC tissues and cells as well as adjacent noncancerous tissues comparing with normal oral epithelial tissues and cells. e knockdown of PER2 facilitated OSCC cell proliferation, migration, and invasion, while PER2 overexpression inhibited these processes
Summary
Oral squamous cell carcinoma (OSCC) is one of the most common tumors in head and neck malignancies with high cancer-related mortality rates worldwide [1]. The mechanisms underlying circadian clock functional involvements in OSCC remain largely unknown. PER2 is a large and multifaceted protein with an incompletely defined domain architecture, whose functional involvement extends beyond its role as a circadian regulator [10, 11]. How PER2 is involved in the progress of OSCC remains largely unknown. E knockdown of PER2 facilitated OSCC cell proliferation, migration, and invasion, while PER2 overexpression inhibited these processes. Our findings demonstrated that PER2, which is obviously downregulated and has an obstacle entering the nucleus in OSCC, gets involved in the processes of OSCC cell proliferation, migration, and invasion
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