VPS33B interacts with NESG1 to modulate EGFR/PI3K/AKT/c-Myc/P53/miR-133a-3p signaling and induce 5-fluorouracil sensitivity in nasopharyngeal carcinoma.
机构：[1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, 510310 Guangzhou, Guangdong, P. R. China.[2]Cancer Center, School of Basic Medical Science, Southern Medical University, 510310 Guangzhou, Guangdong, P. R. China.[3]Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, 511436 Guangzhou, P. R. China.[4]Pediatric Otolaryngology Department, Shenzhen Hospital, Southern Medical University, 518101 Shenzhen, Guangdong, P. R. China南方医科大学深圳医院深圳市康宁医院深圳医学信息中心
The vacuolar protein sorting 33B (VPS33B) was rarely reported in malignant tumors. In this research, we demonstrated that overexpression of VPS33B inhibited proliferation and chemoresistance to fluorouracil (5-FU) in nasopharyngeal carcinoma (NPC) in vivo and in vitro. Mechanistic analysis confirmed that overexpression of VPS33B modulated EGFR/PI3K/AKT/c-Myc/P53 signaling to arrest the cell cycle at G1/S phase. In addition, miR-133a-3p, a tumor-suppressive miRNA, was induced by P53 and directly targeted the EGFR/PI3K/AKT/c-Myc/P53 signaling and thus formed a negative feedback loop. Furthermore, another tumor suppressor, NESG1, interacted with VPS33B by colocalizing in the cytoplasm. The knockdown of NESG1 reversed the inhibitory effects of the overexpression of VPS33B in NPC cells by downregulating the PI3K/AKT/c-Jun-mediated transcription repression. Surprisingly, VPS33B was downregulated in the nicotine-treated and LMP-1-overexpressing NPC cells by targeting PI3K/AKT/c-Jun-mediated signaling. In addition, patients with higher VPS33B expression had a longer overall survival. Our study is the first to demonstrate that VPS33B is negatively regulated by LMP-1 and nicotine and thus suppresses the proliferation of NPC cells by interacting with NESG1 to regulate EGFR/PI3K/AKT/c-Myc/P53/miR-133a-3p signaling in NPC cells.
基金：
This study was supported by the National Nature Science Fund (81071632),
Nature Science Fund of Guangdong Province (No. 2015A030311005, No.
2016A030313628, No. 2017A030313701), Key Scientific Research Projects of
Guangdong Provincial Bureau of Traditional Chinese Medicine (No. 20193010),
the Science and Technology Planning Project of Guangdong Province
(2016A020215233, 20140212), and the Supporting plan for Special Talents in
Guangdong Province (No. 2016TQ03R466).
第一作者机构：[1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, 510310 Guangzhou, Guangdong, P. R. China.[2]Cancer Center, School of Basic Medical Science, Southern Medical University, 510310 Guangzhou, Guangdong, P. R. China.
共同第一作者：
通讯作者：
通讯机构：[1]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, 510310 Guangzhou, Guangdong, P. R. China.[2]Cancer Center, School of Basic Medical Science, Southern Medical University, 510310 Guangzhou, Guangdong, P. R. China.
推荐引用方式(GB/T 7714)：
Liang Zixi,Liu Zhen,Cheng Chao,et al.VPS33B interacts with NESG1 to modulate EGFR/PI3K/AKT/c-Myc/P53/miR-133a-3p signaling and induce 5-fluorouracil sensitivity in nasopharyngeal carcinoma.[J].CELL DEATH & DISEASE.2019,10:doi:10.1038/s41419-019-1457-9.
APA：
Liang Zixi,Liu Zhen,Cheng Chao,Wang Hao,Deng Xiaojie...&Fang Weiyi.(2019).VPS33B interacts with NESG1 to modulate EGFR/PI3K/AKT/c-Myc/P53/miR-133a-3p signaling and induce 5-fluorouracil sensitivity in nasopharyngeal carcinoma..CELL DEATH & DISEASE,10,
MLA：
Liang Zixi,et al."VPS33B interacts with NESG1 to modulate EGFR/PI3K/AKT/c-Myc/P53/miR-133a-3p signaling and induce 5-fluorouracil sensitivity in nasopharyngeal carcinoma.".CELL DEATH & DISEASE 10.(2019)
生物学