RTN2, a new member of circadian clock genes identified by database mining and bioinformatics prediction, is highly expressed in ovarian cancer.

Increasing evidence suggests that core circadian genes have major roles in the carcinogenic mechanisms of multiple human malignancies. Among these genes, the role of reticulon 2 (RTN2) in ovarian cancer (OV) has so far remained elusive. In the present study, circadian clock gene (CCG) aberrations were systematically assessed across malignancies by using Gene Expression Omnibus and The Cancer Genome Atlas data. The results indicated that various core clock genes (ULK1, ATF3, CRY2, CSF3R, DAAM2, GAS7, NPTXR, PPPIR15A and RTN2) had elevated levels in tumors in comparison with normal tissues and their low expression levels were associated with a better prognosis in OV, indicating that they may be potential candidates for novel investigational approaches. The mRNA and protein expression levels of RTN2 in OV were then further analyzed by reverse transcription­quantitative PCR and immunohistochemistry, respectively. The results indicated that RTN2 mRNA and protein levels were increased in OV specimens in comparison with control samples. Differentially expressed CCGs, such as RTN2, were suggested as indicators of asynchronous circadian rhythms in cancer, which may provide a theoretical basis for chrono­therapy.