Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
Department of Thyroid and Hernia Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
J Transl Med. 2024 Oct 8;22(1):914. doi: 10.1186/s12967-024-05668-9.
The heterogeneous nuclear ribonucleoprotein C (HNRNPC) plays a crucial role in tumorigenesis, yet its role in papillary thyroid carcinoma (PTC) remains elusive. Herein, we elucidated the function and molecular mechanism of HNRNPC in PTC tumorigenesis and progression. Our study unveiled a significant upregulation of HNRNPC in PTC, and knockdown of HNRNPC markedly inhibited the proliferation, invasion, and metastasis of BCPAP cells. Furthermore, HNRNPC modulated PKM alternative splicing in BCPAP cells primarily through m6A modification. Additionally, by upregulating PKM2 expression, HNRNPC promoted aerobic glycolysis in BCPAP cells, thereby facilitating malignant progression in PTC. In summary, our findings demonstrate that HNRNPC regulates PKM alternative splicing through m6A methylation modification and promotes the proliferation, invasion and metastasis of PTC through glucose metabolism pathways mediated by PKM2. These discoveries provide new biomarkers for screening and diagnosing PTC patients and offer novel therapeutic targets for personalized treatment strategies.
异质核核糖核蛋白 C（HNRNPC）在肿瘤发生中起着至关重要的作用，但它在甲状腺乳头状癌（PTC）中的作用仍不清楚。在此，我们阐明了 HNRNPC 在 PTC 发生和进展中的功能和分子机制。我们的研究揭示了 HNRNPC 在 PTC 中的显著上调，敲低 HNRNPC 可显著抑制 BCPAP 细胞的增殖、侵袭和转移。此外，HNRNPC 通过 m6A 修饰主要调节 BCPAP 细胞中的 PKM 可变剪接。此外，通过上调 PKM2 的表达，HNRNPC 促进了 BCPAP 细胞的有氧糖酵解，从而促进了 PTC 的恶性进展。综上所述，我们的研究结果表明，HNRNPC 通过 m6A 甲基化修饰调节 PKM 可变剪接，并通过 PKM2 介导的葡萄糖代谢途径促进 PTC 的增殖、侵袭和转移。这些发现为 PTC 患者的筛查和诊断提供了新的生物标志物，并为个性化治疗策略提供了新的治疗靶点。
