RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding

doi:10.1186/s13046-023-02874-z

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	RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding
	Lin, Ying 1; Wu, Yun 2; Zhang, Qiangzu 3; Tu, Xunwei 1; Chen, Sufang 1; Pan, Junfan 1; Xu, Nengluan 1; Lin, Ming 1; She, Peiwei 4; Niu, Gang 3; Chen, Yusheng 1; Li, Hongru 1,5
	2024-01-02
发表期刊	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
卷号	43 期号:1 页码:15
摘要	Background Ceramide metabolism is crucial in the progress of brain metastasis (BM). However, it remains unexplored whether targeting ceramide metabolism may arrest BM. Methods RNA sequencing was applied to screen different genes in primary and metastatic foci and whole-exome sequencing (WES) to seek crucial abnormal pathway in BM + and BM-patients. Cellular arrays were applied to analyze the permeability of blood-brain barrier (BBB) and the activation or inhibition of pathway. Database and Co-Immunoprecipitation (Co-IP) assay were adopted to verify the protein-protein interaction. Xenograft and zebrafish model were further employed to verify the cellular results. Results RNA sequencing and WES reported the involvement of RPTOR and ceramide metabolism in BM progress. RPTOR was significantly upregulated in BM foci and increased the permeability of BBB, while RPTOR deficiency attenuated the cell invasiveness and protected extracellular matrix. Exogenous RPTOR boosted the SPHK2/S1P/STAT3 cascades by binding YY1, in which YY1 bound to the regions of SPHK2 promoter (at -353 similar to -365 nt), further promoting the expression of SPHK2. The latter was rescued by YY1 RNAi. Xenograft and zebrafish model showed that RPTOR blockade suppressed BM of non-small cell lung cancer (NSCLC) and impaired the SPHK2/S1P/STAT3 pathway. Conclusion RPTOR is a key driver gene in the brain metastasis of lung cancer, which signifies that RPTOR blockade may serve as a promising therapeutic candidate for clinical application.
关键词	Non-small cell lung cancer Brain metastasis RPTOR SPHK2 S1P
DOI	10.1186/s13046-023-02874-z
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:001134651400001
出版者	BMC
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/38442
专题	中国科学院计算技术研究所
通讯作者	Niu, Gang; Chen, Yusheng; Li, Hongru
作者单位	1.Fujian Med Univ, Fujian Prov Hosp, Shengli Clin Med Coll, Dept Resp & Crit Care Med, Fuzhou 350001, Fujian, Peoples R China 2.Fujian Prov Hosp, Dept Gen Practice Med, Fuzhou 350001, Peoples R China 3.Chinese Acad Sci, Inst Comp Technol, High Performance Comp Res Ctr, Beijing 100095, Peoples R China 4.Fujian Prov Hosp, Ctr Expt Res Clin Med, Fuzhou 350001, Fujian, Peoples R China 5.Fujian Med Univ, Fujian Prov Hosp, Fujian Prov Key Lab Med Big Data Engn, Shengli Clin Coll, Fuzhou 350001, Fujian, Peoples R China
推荐引用方式 GB/T 7714	Lin, Ying,Wu, Yun,Zhang, Qiangzu,et al. RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2024,43(1):15.
APA	Lin, Ying.,Wu, Yun.,Zhang, Qiangzu.,Tu, Xunwei.,Chen, Sufang.,...&Li, Hongru.(2024).RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,43(1),15.
MLA	Lin, Ying,et al."RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 43.1(2024):15.