Cyclin-dependent kinase inhibitor 3 promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting P27.

Cyclin-dependent kinase inhibitor 3 promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting P27.

Oncol Res. 2017 Jan 20;:

Authors: Wang H, Chen H, Zhou H, Yu W, Lu Z

Abstract
Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy with high invasion which arises from the nasopharynx epithelium. Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the dual-specificity protein phosphatase family which plays a key role in regulating cell division. Abnormal expression of CDKN3 has been found in numerous types of cancer. In the current study, we explored the possible role of CDKN3 in cell proliferation, invasion ability and radiosensitivity in NPC cells. We reported that CDKN3 was upregulated and P27 was downregulated in NPC tissues and associated with worse patient prognosis. In addition, downregulation of CDKN3 and upregulation of P27 decreased cell proliferation, induced cell cycle arrest, increased apoptosis, decreased cell invasion and enhanced radiosensitivity. Silence of P27 significantly inhibited these effects of knockdown of CDKN3. Moreover, downregulation of CDKN3 and upregulation of P27 inhibited the increase of tumor volume and weight in implanted tumors, decreased the phospshorylation of Akt and increased the expression of cleaved caspase 3 in tumors. Moreover, CDKN3 expression was inversely correlated with P27 expression in NPC patients. Knockdown of CDKN3 increased P27 expression. Silence of P27 markedly inhibited the the effects of CDKN3 on cell proliferation, cell cycle progression, apoptosis, invasion and radiosensitivity. These results demonstrated that upregulation of P27 was involved in knockdown of CDKN3-induced decrease of cell proliferation, increase of cell cycle arrest and apoptosis, decrease of invasion and increase of radiosensitivity. The results demonstrated that CDKN3/P27 axis may be a novel target for the treatment of NPC.

PMID: 28109073 [PubMed - as supplied by publisher]

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