Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China.
Department of Otorhinolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital, Harbin Medical University, Daqing 163316, China.
Int J Biol Sci. 2023 Feb 22;19(5):1382-1400. doi: 10.7150/ijbs.80921. eCollection 2023.
Translation machinery associated 7 homolog (TMA7) is closely related to proliferation-related diseases. However, the function and regulatory mechanism of TMA7 in laryngeal squamous cell carcinoma (LSCC) remain unclear. The present study aimed to investigate the effect of TMA7 on the occurrence and development of LSCC and to study the mechanism of TMA7. TMA7 is upregulated in LSCC tissues and associated with poor prognosis. After TMA7 downregulation, the autophagy level was increased, and the proliferation, migration, and invasion of LSCC cells were inhibited. The m6A methylated reader IGF2BP3 enhanced the stability of TMA7 and reduced the level of autophagy. TMA7 interacted directly with UBA2. Furthermore, the activation of the IGF2BP3-regulated TMA7-UBA2-PI3K pathway is the primary mechanism by which TMA7 inhibits autophagy and promotes the progression of LSCC. The current study revealed that IGF2BP3-mediated TMA7 m6A modification promotes LSCC progression and cisplatin-resistance through UBA2-PI3K pathway, providing new insights into the autophagy-related mechanism, potential biomarkers, and therapeutic targets for LSCC.
翻译机器相关同源物 7（TMA7）与增殖相关疾病密切相关。然而，TMA7 在喉鳞状细胞癌（LSCC）中的功能和调节机制尚不清楚。本研究旨在探讨 TMA7 对 LSCC 发生发展的影响，并研究 TMA7 的作用机制。TMA7 在 LSCC 组织中上调，并与不良预后相关。下调 TMA7 后，自噬水平增加，LSCC 细胞的增殖、迁移和侵袭受到抑制。m6A 甲基化阅读器 IGF2BP3 增强了 TMA7 的稳定性，降低了自噬水平。TMA7 与 UBA2 直接相互作用。此外，IGF2BP3 调节的 TMA7-UBA2-PI3K 通路的激活是 TMA7 抑制自噬并促进 LSCC 进展的主要机制。本研究揭示了 IGF2BP3 介导的 TMA7 m6A 修饰通过 UBA2-PI3K 通路促进 LSCC 的进展和顺铂耐药性，为 LSCC 的自噬相关机制、潜在生物标志物和治疗靶点提供了新的见解。
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