THOC3 通过与 YBX1 相互作用促进肺鳞癌细胞的进展通过 PFKFB4 mRNA 修饰。
THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification.
机构信息
Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, China.
Department of Oncology, the Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China.
出版信息
Cell Death Dis. 2023 Jul 27;14(7):475. doi: 10.1038/s41419-023-06008-3.
The THO complex (THOC) is ubiquitously involved in RNA modification and various THOC proteins have been reported to regulate tumor development. However, the role of THOC3 in lung cancer remains unknown. In this study, we identified that THOC3 was highly expressed in lung squamous cell carcinoma (LUSC) and negatively associated with prognosis. THOC3 knockdown inhibited LUSC cell growth, migration, and glycolysis. THOC3 expression was regulated by TRiC proteins, such as CCT8 and CCT6A, which supported protein folding. Furthermore, THOC3 could form a complex with YBX1 to promote PFKFB4 transcription. THOC3 was responsible for exporting PFKFB4 mRNA to the cytoplasm, while YBX1 ensured the stability of PFKFB4 mRNA by recognizing m5C sites in its 3'UTR. Downregulation of PFKFB4 suppressed the biological activities of LUSC. Collectively, these findings suggest that THOC3, folded by CCT proteins can collaborate with YBX1 to maintain PFKFB4 expression and facilitate LUSC development. Therefore, THOC3 could be considered as a novel promising therapeutic target for LUSC.
THO 复合物（THOC）广泛参与 RNA 修饰，已有报道称多种 THOC 蛋白可调节肿瘤的发生。然而，THOC3 在肺癌中的作用尚不清楚。在本研究中，我们发现 THOC3 在肺鳞癌（LUSC）中高表达，并与预后呈负相关。THOC3 敲低抑制了 LUSC 细胞的生长、迁移和糖酵解。THOC3 的表达受 TRiC 蛋白（如 CCT8 和 CCT6A）调节，这些蛋白支持蛋白质折叠。此外，THOC3 可以与 YBX1 形成复合物，促进 PFKFB4 转录。THOC3 负责将 PFKFB4 mRNA 输出到细胞质，而 YBX1 通过识别其 3'UTR 中的 m5C 位点来确保 PFKFB4 mRNA 的稳定性。PFKFB4 的下调抑制了 LUSC 的生物学活性。总之，这些发现表明，由 CCT 蛋白折叠的 THOC3 可以与 YBX1 合作维持 PFKFB4 的表达，促进 LUSC 的发展。因此，THOC3 可被视为治疗 LUSC 的一种有前途的新靶点。
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