JMJD3 suppresses stem cell-like characteristics in breast cancer cells by downregulation of Oct4 independently of its demethylase activity
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Jing Xun1, Dekun Wang1, Long Shen1, Junbo Gong2, Ruifang Gao1, Lingfang Du1, Antao Chang1, Xiangrong Song3, Rong Xiang1, Xiaoyue Tan1
1College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China
2Tianjin Key Laboratory of Modern Drug Delivery and High Efficiency in Tianjin University, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
3State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
Xiaoyue Tan, email: [email protected]
Keywords: JMJD3, Oct4, cancer stem cell-like characteristic, PHF20, paricalcitol
Received: October 11, 2016 Accepted: January 24, 2017 Published: February 26, 2017
Epigenetic regulator JMJD3 plays an important role in both tumor progression and somatic cell reprogramming. Here, we explored the effect of JMJD3 on the stem cell-like characteristics of breast cancer and its underlying mechanism involving stemness-related transcription factor Oct4. Our data revealed that, in breast cancer cells lines and an orthotopic xenograph mouse model of breast cancer, ectopic overexpression of JMJD3 suppressed stem cell-like characteristics of breast cancer cells, whereas knockdown of JMJD3 promoted these characteristics. Oct4 mediated the suppressive effects of JMJD3 on the stemness of breast cancer cells. The inhibitory effect of JMJD3 on Oct4 was independent of demethylase activity, but mediated via degradation of PHF20. Furthermore, we applied an agonist of the vitamin D receptor, paricalcitol, and found that it induced JMJD3 in breast cancer cells. Our data showed that administration of paricalcitol suppressed stem cell-like characteristics and Oct4 expression. Taken together, JMJD3 inhibits the stem cell-like characteristics in breast cancer by suppression of stemness factor Oct4 in a PHF20-dependent manner. Administration of paricalcitol leads to upregulation of JMJD3 that suppresses Oct4 expression and the stem cell-like characteristics in breast cancer.
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