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

文献类型：期刊论文

作者Lin, Ying5; Wu, Yun4; Zhang, Qiangzu3; Tu, Xunwei5; Chen, Sufang5; Pan, Junfan5; Xu, Nengluan5; Lin, Ming5; She, Peiwei2; Niu, Gang3
刊名JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
出版日期2024-01-02
卷号43期号:1页码:15
关键词Non-small cell lung cancer Brain metastasis RPTOR SPHK2 S1P
DOI10.1186/s13046-023-02874-z
英文摘要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.
资助项目National Natural Science Foundation of China
WOS研究方向Oncology
语种英语
WOS记录号WOS:001134651400001
出版者BMC
源URL[http://119.78.100.204/handle/2XEOYT63/38441]  
专题中国科学院计算技术研究所期刊论文_英文
通讯作者Niu, Gang; Chen, Yusheng; Li, Hongru
作者单位1.Fujian Med Univ, Fujian Prov Hosp, Fujian Prov Key Lab Med Big Data Engn, Shengli Clin Coll, Fuzhou 350001, Fujian, Peoples R China
2.Fujian Prov Hosp, Ctr Expt Res Clin Med, Fuzhou 350001, Fujian, Peoples R China
3.Chinese Acad Sci, Inst Comp Technol, High Performance Comp Res Ctr, Beijing 100095, Peoples R China
4.Fujian Prov Hosp, Dept Gen Practice Med, Fuzhou 350001, Peoples R China
5.Fujian Med Univ, Fujian Prov Hosp, Shengli Clin Med Coll, Dept Resp & Crit Care Med, 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.

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来源：计算技术研究所

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