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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
WTAP 增强膀胱癌中 YTHDF2 引起的 SYTL1 mRNA 不稳定性
英文原题：WTAP enhances the instability of SYTL1 mRNA caused by YTHDF2 in bladder cancer.
查看英文原题
WTAP enhances the instability of SYTL1 mRNA caused by YTHDF2 in bladder cancer.
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研究概要
WTAP 通过 YTHDF2 介导的 m6A 甲基化促进 SYTL1 mRNA 降解，从而抑制 NK 细胞对 BCa 细胞的抗肿瘤反应。
中文摘要
背景
膀胱癌（BCa）是人类最常见的癌症。已有研究描述了m6A修饰与自然杀伤（NK）细胞抗肿瘤作用在BCa中的关联。本研究旨在探讨m6A调节因子如何调控BCa中的SYTL1表达，以及其与NK细胞抗肿瘤作用的关系。
方法
通过生物信息学分析研究SYTL1在BCa中的预后作用，并分析SYTL1表达与NK细胞的相关性。采用RT-qPCR、细胞毒性检测、Western blot和ELISA评估SYTL1对NK-92细胞抗肿瘤反应的影响；采用RT-qPCR、RIP-qPCR、ELISA及放线菌素D处理研究WTAP、YTHDF2与SYTL1之间的关系。最后，在体内验证WTAP和SYTL1对BCa肿瘤生长及NK细胞抗肿瘤反应的影响。
结果
SYTL1在BCa组织中表达降低，具有预后意义，并与NK细胞介导的抗肿瘤反应相关。NK-92细胞可杀伤BCa细胞；BCa细胞中过表达SYTL1后，这种作用进一步增强，同时LDH、NKG2D、NKp30、NKp44及IFN-γ水平均升高。WTAP通过YTHDF2促进SYTL1 mRNA降解。WTAP和YTHDF2会削弱NK细胞对BCa的抗肿瘤反应。SYTL1可抑制小鼠BCa进展，同时增强NK细胞抗肿瘤反应。
结论
WTAP通过促进YTHDF2介导的m6A甲基化及SYTL1 mRNA降解，抑制NK细胞对膀胱癌细胞的抗肿瘤反应。
展开英文摘要原文
BACKGROUND
Bladder cancer (BCa) is the most frequent type of cancer in humans. The association between m6A modification and the anti-tumor effects of natural killer (NK) cells has been described in BCa. This study intended to investigate the implications of m6A regulators in modulating SYTL1 expression in BCa and the association with the anti-tumor effects of NK cells.
METHODS
The prognostic role of SYTL1 in BCa was investigated using bioinformatics analysis, and the correlation between SYTL1 expression and NK cells was analyzed. The effects of SYTL1 on the anti-tumor response of NK-92 cells were examined by RT-qPCR, cytotoxicity, western blot, and ELISA assays. The relationships among WTAP, YTHDF2, and SYTL1 were investigated by RT-qPCR, RIP-qPCR, ELISA, and actinomycin D treatment. Finally, the effects of WTAP and SYTL1 on BCa tumor growth and the anti-tumor response of NK cells were verified in vivo .
RESULTS
SYTL1 was reduced in BCa tissues and had a prognostic significance, which was related to NK cell-mediated anti-tumor responses. NK-92 cells produced toxicity to BCa cells, which was further enhanced by SYTL1 overexpression in BCa cells through prompting LDH, NKG2D, NKp30, and NKp44 and IFN- levels. WTAP enhanced the degradation of the SYTL1 mRNA by YTHDF2. WTAP and YTHDF2 impaired the anti-tumor response of NK cells in BCa. SYTL1 inhibited the BCa progression in mice while enhancing the anti-tumor response of NK cells.
CONCLUSIONS
WTAP inhibited the anti-tumor response of NK cells to BCa cells by promoting the degradation of SYTL1 mRNA through YTHDF2-mediated m6A methylation.
论文信息
- 作者
- Wang J、Luo J、Wu X、Li Z
- 第一作者单位
- Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, PR China.China
- 通讯作者单位
- Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, PR China. zhuo_L8232@126.com.China
- 期刊
- Histology and histopathology2024 May
- 原文标识
- PubMed 37933909 · DOI 10.14670/HH-18-671