HNRNPC modulates PKM alternative splicing via m6A methylation, upregulating PKM2 expression to promote aerobic glycolysis in papillary thyroid carcinoma and drive malignant progression

Autor: Shikuo Rong, Bao Dai, Chunrong Yang, Ziteng Lan, Linhe Wang, Lei Xu, Weijian Chen, Jian Chen, Zeyu Wu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Translational Medicine, Vol 22, Iss 1, Pp 1-18 (2024)
Druh dokumentu: article
ISSN: 1479-5876
DOI: 10.1186/s12967-024-05668-9
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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