Mo Anwei, Wang Huaiwen
Department of Oncology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou City, Hainan, 570311, China.
Department of Anorectal Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou City, Hainan, 570311, China.
Biomark Med. 2024;18(21-22):945-955. doi: 10.1080/17520363.2024.2416886. Epub 2024 Oct 29.
Wilms' tumor 1-associating protein (WTAP), plays a part in colorectal cancer (CRC) progression. However, it is not yet known how WTAP affects cancer progression by influencing leukocyte rich repeat containing proteins (NLR) - family members 3 (NLRP3) - related inflammasomes. We first validated the expression of WTAP in CRC at the tissue and cellular levels. Subsequently, by transfecting si-NC and si-WTAP into cells, we verified functions of WTAP in proliferation, invasion, migration and apoptosis of CRC cells. Finally, we analyzed the N6-methyladenosine (m6A) modification of NLRP3 by WTAP using methylated RNA immunoprecipitation (MeRIP)-qPCR technology, confirming that WTAP mediated the repression of NLRP3 inflammasome and the malignant progression of tumor cells. WTAP was substantially upregulated in CRC tissues and cells. WTAP reinforced the migration, proliferation and invasion ability of CRC cells, and repressed apoptosis. Mechanistically, WTAP mediated the m6A modification of NLRP3, which suppressed the expression of NLRP3 and dampened the NLRP3/Caspase-1/GSDMD axis activation as well as pyroptosis, thereby facilitating the malignant progression of CRC. WTAP mediates m6A modification to modulate the repression of the NLRP3/Caspase-1/GSDMD axis in pyroptosis, reinforcing the malignant progression of CRC.
肾母细胞瘤1相关蛋白（WTAP）在结直肠癌（CRC）进展中发挥作用。然而，WTAP如何通过影响富含白细胞重复序列蛋白（NLR）家族成员3（NLRP3）相关炎性小体来影响癌症进展尚不清楚。我们首先在组织和细胞水平上验证了WTAP在CRC中的表达。随后，通过将si-NC和si-WTAP转染到细胞中，我们验证了WTAP在CRC细胞增殖、侵袭、迁移和凋亡中的功能。最后，我们使用甲基化RNA免疫沉淀（MeRIP）-qPCR技术分析了WTAP对NLRP3的N6-甲基腺苷（m6A）修饰，证实WTAP介导了NLRP3炎性小体的抑制和肿瘤细胞的恶性进展。WTAP在CRC组织和细胞中显著上调。WTAP增强了CRC细胞的迁移、增殖和侵袭能力，并抑制了凋亡。机制上，WTAP介导了NLRP3的m6A修饰，抑制了NLRP3的表达，减弱了NLRP3/Caspase-1/GSDMD轴的激活以及细胞焦亡，从而促进了CRC的恶性进展。WTAP介导m6A修饰以调节细胞焦亡中NLRP3/Caspase-1/GSDMD轴的抑制，增强了CRC的恶性进展。
