USP22 down-regulation facilitates human retinoblastoma cell aging and apoptosis via inhibiting TERT/P53 pathway.

OBJECTIVE: Retinoblastoma is the most common malignant intraocular tumor in childhood, and still lacks effective treatment. The immortality of tumor cell can be attributed to elevated telomerase activity, which has been considered as tumor marker and treatment target. USP22 is one of the important targets for inhibiting tumor growth, but clear illustration regarding its effects of telomerase, tumor cell immortality and retinoblastoma cell aging or apoptosis via suppressing TERT/P53 signal pathway remains to be elusive.

MATERIALS AND METHODS: MTT was used for describing cell proliferation, and Western blot was used to test protein expression level of USP22, TERT and P53. RT-qPCR was used to test USP22 mRNA level, followed by TRAP method to detect telomerase activity. Flow cytometry and comet assay were used to quantify cell apoptosis and DNA damage. Cell aging was measured by β-galactosidase.

RESULTS: The overexpression of USP22 significantly enhanced cell proliferation potency and telomerase activity, elevated TERT expression level, inhibited p53 expression and cell aging, as well as decreased cell apoptosis or DNA damage. Down-regulation of USP22 contributed to opposite effects.

CONCLUSIONS: USP22 played an important role in retinoblastoma cell proliferation/aging and apoptosis. The reduction of USP22 expression facilitated human retinoblastoma cell aging or apoptosis via suppressing TERT/P53 signal pathway. USP22, thus, may work as a target for treating retinoblastoma.