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Theranostics 2017; 7(5):1389-1406. doi:10.7150/thno.17647 This issue Cite

Research Paper

Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1

Teng-Jian Zhou1, Shi-Li Zhang1, Cheng-Yong He1, Qun-Ying Zhuang1, Pei-Yu Han1, Sheng-Wei Jiang1, Huan Yao1, Yi-Jun Huang2, Wen-Hua Ling3, Yu-Chun Lin1✉, Zhong-Ning Lin1✉

1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen Fujian 361102, PR China;
2. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China;
3. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.

✉ Corresponding authors: Y. Lin and Z. Lin, linychedu.cn; linzhnedu.cn. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiang'an south Road, Xiamen, 361102, China.

Citation:
Zhou TJ, Zhang SL, He CY, Zhuang QY, Han PY, Jiang SW, Yao H, Huang YJ, Ling WH, Lin YC, Lin ZN. Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1. Theranostics 2017; 7(5):1389-1406. doi:10.7150/thno.17647. https://www.thno.org/v07p1389.htm
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Abstract

Graphic abstract

Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in NPC tissues. Using both overexpression and knockdown of COX-2, we demonstrated that the localization of COX-2 at mitochondria promotes the stemness of NPC by recruiting the mitochondrial translocation of p53, increasing the activity of Drp1 and inducing mitochondrial fisson. Inhibition of the expression or the activity of Drp1 by siRNA or Mdivi-1 downregulates the stemness of NPC. The present study also found that inhibition of mitochondrial COX-2 with resveratrol (RSV), a natural phytochemical, increased the sensitivity of NPC to 5-fluorouracil (5-FU), a classical chemotherapy drug for NPC. The underlying mechanism is that RSV suppresses mitochondrial COX-2, thereby reducing NPC stemness by inhibiting Drp1 activity as demonstrated in both the in vitro and the in vivo studies. Taken together, the results of this study suggest that mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC. Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical treatment of therapy-resistant NPC.

Keywords: mitochondrial cyclooxygenase-2, nasopharyngeal carcinoma, cancer stemness, dynamin-related protein 1, mitochondrial quality control.

Citation styles

APA
Zhou, T.J., Zhang, S.L., He, C.Y., Zhuang, Q.Y., Han, P.Y., Jiang, S.W., Yao, H., Huang, Y.J., Ling, W.H., Lin, Y.C., Lin, Z.N. (2017). Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1. Theranostics, 7(5), 1389-1406. https://doi.org/10.7150/thno.17647.

ACS
Zhou, T.J.; Zhang, S.L.; He, C.Y.; Zhuang, Q.Y.; Han, P.Y.; Jiang, S.W.; Yao, H.; Huang, Y.J.; Ling, W.H.; Lin, Y.C.; Lin, Z.N. Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1. Theranostics 2017, 7 (5), 1389-1406. DOI: 10.7150/thno.17647.

NLM
Zhou TJ, Zhang SL, He CY, Zhuang QY, Han PY, Jiang SW, Yao H, Huang YJ, Ling WH, Lin YC, Lin ZN. Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1. Theranostics 2017; 7(5):1389-1406. doi:10.7150/thno.17647. https://www.thno.org/v07p1389.htm

CSE
Zhou TJ, Zhang SL, He CY, Zhuang QY, Han PY, Jiang SW, Yao H, Huang YJ, Ling WH, Lin YC, Lin ZN. 2017. Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1. Theranostics. 7(5):1389-1406.

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