Open Access

ARTICLE

Cyclin-Dependent Kinase Inhibitor 3 Promotes Cancer Cell Proliferation and Tumorigenesis in Nasopharyngeal Carcinoma by Targeting p27

Huimin Wang^*, Hexin Chen^†, Hang Zhou^*, Wenfa Yu^*, Zhenmin Lu^*

* Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P.R. China
† Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China

Oncology Research 2017, 25(9), 1431-1440. https://doi.org/10.3727/096504017X14835311718295

Abstract

Nasopharyngeal carcinoma (NPC) is a common malignancy of the head and neck that arises from the nasopharynx epithelium and is highly invasive. Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the dualspecificity 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, ability to invade, and radiosensitivity in NPC cells. We reported that CDKN3 was upregulated and p27 was downregulated in NPC tissues and is associated with a worse prognosis for patients. In addition, downregulation of CDKN3 and upregulation of p27 decreased cell proliferation, induced cell cycle arrest, increased apoptosis, decreased cell invasion, and enhanced radiosensitivity. Silencing of p27 significantly inhibited the effects of the knockdown of CDKN3. Moreover, downregulation of CDKN3 and upregulation of p27 inhibited the increase in tumor volume and weight in implanted tumors, decreased the phosphorylation of Akt, and increased the expression of cleaved caspase 3 in tumors. CDKN3 expression was also inversely correlated with p27 expression in NPC patients. Knockdown of CDKN3 increased p27 expression. Silencing of p27 markedly inhibited the effects of CDKN3 on cell proliferation, cell cycle progression, apoptosis, invasion, and radiosensitivity. These results demonstrate that upregulation of p27 is involved in the knockdown of CDKN3-induced decrease in cell proliferation, increase in cell cycle arrest and apoptosis, decrease in invasion, and increase in radiosensitivity. The results demonstrate that the CDKN3/p27 axis may be a novel target in the treatment of NPC.

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