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BPIFB1 inhibits vasculogenic mimicry via downregulation of GLUT1-mediated H3K27 acetylation in nasopharyngeal carcinoma

Oncogene volume 41, pages 233–245 (2022)Cite this article

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Abstract

Nasopharyngeal carcinoma (NPC) demonstrates significant regional differences and a high incidence in Southeast Asia and Southern China. Bactericidal/permeability-increasing-fold- containing family B member 1 (BPIFB1) is a relatively specific and highly expressed protein in the nasopharyngeal epithelium. BPIFB1 expression is substantially downregulated in NPC and is significantly associated with poor prognosis in patients with NPC. However, the specific molecular mechanism by which BPIFB1 regulates NPC is not well understood. In this study, we found that BPIFB1 inhibits vasculogenic mimicry by regulating the metabolic reprogramming of NPC. BPIFB1 decreases GLUT1 transcription by downregulating the JNK/AP1 signaling pathway. Altered glycolysis reduces the acetylation level of histone and decreases the expression of vasculogenic mimicry-related genes, VEGFA, VE-cadherin, and MMP2, ultimately leading to the inhibition of vasculogenic mimicry. To our knowledge, this is the first report on the role and specific mechanism of BPIFB1 as a tumor suppressor gene involved in regulating glycolysis and vasculogenic mimicry in NPC. Overall, these results provide a new therapeutic target for NPC diagnosis and treatment.

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Fig. 1: BPIFB1 inhibits vasculogenic mimicry (VM) in nasopharyngeal carcinoma.
Fig. 2: BPIFB1 inhibits glycolysis by downregulating GLUT1.
Fig. 3: BPIFB1 inhibits VM formation by downregulating GLUT1.
Fig. 4: BPIFB1 inhibits H3K27 acetylation by downregulating GLUT1.
Fig. 5: BPIFB1 decreases GLUT1 transcription by downregulating the JNK/AP1 pathway.
Fig. 6: BPIFB1 reduces VM formation via GLUT1 downregulation in vivo.
Fig. 7: Relationship between BPIFB1 and GLUT1, VEGFA, VE-cadherin, and MMP2 in NPC tissues.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (81903138, 81972776, U20A20367), the Overseas Expertize Introduction Project for Discipline Innovation (111 Project, No. 111-2-12), the Natural Science Foundation of Hunan Province (2019JJ50778, 2019JJ50872, 2020JJ4766).

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Authors and Affiliations

  1. NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China

    Xianjie Jiang, Yi He, Bo Xiang, Ming Zhou, Qianjin Liao, Xiaoling Li, Guiyuan Li, Wei Xiong & Zhaoyang Zeng

  2. Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China

    Xianjie Jiang, Xiangying Deng, Jie Wang, Yongzhen Mo, Lei Shi, Fang Wei, Yumin Wang, Can Guo, Bo Xiang, Ming Zhou, Xiaoling Li, Guiyuan Li, Wei Xiong & Zhaoyang Zeng

  3. Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Lei Shi & Zhaojian Gong

  4. Department of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Shanshan Zhang & Fang Xiong

  5. Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Yong Li

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  1. Xianjie Jiang
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Contributions

XJ performed all Experiments; ZZ designed this study; XD, JW, YM and LS collected tissue samples and the clinical data; FW, SZ, ZG and YH gave guidance on experimental methods; FX, YW, CG, BX, MZ, QL, XL, GL, WX analyzed and interpreted the data; XJ and ZZ drafted the paper. All authors read and approved the final paper.

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Correspondence to Zhaoyang Zeng.

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Jiang, X., Deng, X., Wang, J. et al. BPIFB1 inhibits vasculogenic mimicry via downregulation of GLUT1-mediated H3K27 acetylation in nasopharyngeal carcinoma. Oncogene 41, 233–245 (2022). https://doi.org/10.1038/s41388-021-02079-8

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