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논문 기본 정보

자료유형
학술저널
저자정보
Zhao Jingyi (the First Affiliated Hospital of Zhengzhou University) Li Bingyan (the First Affiliated Hospital of Zhengzhou University) Ren Yongxia (Huaihe Hospital of Henan University) Liang Tiansong (the First Affiliated Hospital of Zhengzhou University) Wang Juan (the First Affiliated Hospital of Zhengzhou University) Zhai Suna (the First Affiliated Hospital of Zhengzhou University) Zhang Xiqian (the First Affiliated Hospital of Zhengzhou University) Zhou Pengcheng (the First Affiliated Hospital of Zhengzhou University) Zhang Xiangxian (the First Affiliated Hospital of Zhengzhou University) Pan Yuanyuan (the First Affiliated Hospital of Zhengzhou University) Gao Fangfang (the First Affiliated Hospital of Zhengzhou University) Zhang Sulan (Institute of Radiation Therapy and Tumor Critical Care of Zhengzhou University) Li Liming (Henan Key Laboratory of Molecular Radiotherapy) Yang Yongqiang (the First Affiliated Hospital of Zhengzhou University) Deng Xiaoyu (the First Affiliated Hospital of Zhengzhou University) Li Xiaole (the First Affiliated Hospital of Zhengzhou University) Chen Linhui (the First Affiliated Hospital of Zhengzhou University) Yang Daoke (the First Affiliated Hospital of Zhengzhou University) Zheng Yingjuan (the First Affiliated Hospital of Zhengzhou University)
저널정보
대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제53권
발행연도
2021.8
수록면
1 - 11 (11page)
DOI
10.1038/s12276-021-00657-0

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Compelling evidence has indicated the vital role of lysine-specific demethylase 4?A (KDM4A), hypoxia-inducible factor-1α (HIF1α) and the mechanistic target of rapamycin (mTOR) signaling pathway in nasopharyngeal carcinoma (NPC). Therefore, we aimed to investigate whether KDM4A affects NPC progression by regulating the HIF1α/DDIT4/mTOR signaling pathway. First, NPC and adjacent tissue samples were collected, and KDM4A protein expression was examined by immunohistochemistry. Then, the interactions among KDM4A, HIF1α and DDIT4 were assessed. Gain- and loss-of-function approaches were used to alter KDM4A, HIF1α and DDIT4 expression in NPC cells. The mechanism of KDM4A in NPC was evaluated both in vivo and in vitro via RT-qPCR, Western blot analysis, MTT assay, Transwell assay, flow cytometry and tumor formation experiments. KDM4A, HIF1α, and DDIT4 were highly expressed in NPC tissues and cells. Mechanistically, KDM4A inhibited the enrichment of histone H3 lysine 9 trimethylation (H3K9me3) in the HIF1α promoter region and thus inhibited the methylation of HIF1α to promote HIF1α expression, thus upregulating DDIT4 and activating the mTOR signaling pathway. Overexpression of KDM4A, HIF1α, or DDIT4 or activation of the mTOR signaling pathway promoted SUNE1 cell proliferation, migration, and invasion but inhibited apoptosis. KDM4A silencing blocked the mTOR signaling pathway by inhibiting the HIF1α/DDIT4 axis to inhibit the growth of SUNE1 cells in vivo. Collectively, KDM4A silencing could inhibit NPC progression by blocking the activation of the HIF1α/DDIT4/mTOR signaling pathway by increasing H3K9me3, highlighting a promising therapeutic target for NPC.

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