Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, PR China.
Histol Histopathol. 2024 May;39(5):633-646. doi: 10.14670/HH-18-671. Epub 2023 Oct 23.
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.
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 .
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-γ 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.
WTAP inhibited the anti-tumor response of NK cells to BCa cells by promoting the degradation of SYTL1 mRNA through YTHDF2-mediated m6A methylation.
膀胱癌（BCa）是人类最常见的癌症类型。m6A 修饰与自然杀伤（NK）细胞的抗肿瘤作用之间的关联已在 BCa 中描述。本研究旨在研究 m6A 调节剂在调节 BCa 中 SYTL1 表达中的意义及其与 NK 细胞抗肿瘤作用的关联。
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。通过 RT-qPCR、细胞毒性、Western blot 和 ELISA 检测 SYTL1 对 NK-92 细胞抗肿瘤反应的影响。通过 RT-qPCR、RIP-qPCR、ELISA 和放线菌素 D 处理研究 WTAP、YTHDF2 和 SYTL1 之间的关系。最后，验证 WTAP 和 SYTL1 对 BCa 肿瘤生长和 NK 细胞抗肿瘤反应的影响。
SYTL1 在 BCa 组织中减少，具有预后意义，与 NK 细胞介导的抗肿瘤反应有关。NK-92 细胞对 BCa 细胞产生毒性，通过在 BCa 细胞中过表达 SYTL1 进一步增强，通过促使 LDH、NKG2D、NKp30 和 NKp44 以及 IFN-γ 水平。WTAP 通过 YTHDF2 增强 SYTL1 mRNA 的降解。WTAP 和 YTHDF2 损害了 BCa 中 NK 细胞的抗肿瘤反应。SYTL1 抑制小鼠中 BCa 的进展，同时增强 NK 细胞的抗肿瘤反应。
WTAP 通过 YTHDF2 介导的 m6A 甲基化促进 SYTL1 mRNA 的降解，从而抑制 NK 细胞对 BCa 细胞的抗肿瘤反应。
