N6-甲基腺苷 (m6A) 读取器 HNRNPA2B1 加速宫颈癌细胞的有氧糖酵解。
N6-methyladenosine (m6A) reader HNRNPA2B1 accelerates the cervical cancer cells aerobic glycolysis.
发表日期:2024 Oct 19
作者:
Mengke Wen, Na Yi, Bulabiyamu Mijiti, Shihong Zhao, Guqun Shen
来源:
Epigenetics & Chromatin
摘要:
N6-甲基腺苷(m6A)修饰是一种较常见的表观遗传修饰,主要存在于mRNA中。越来越多的研究表明m6A对人类癌症的重要作用。本研究旨在探讨 hnRNPA2B1 和 m6A 依赖性机制在宫颈癌中的作用。 hnRNPA2B1升高提示宫颈癌患者预后不良。强加hnRNPA2B1可减少宫颈癌细胞的凋亡,并加速体外宫颈癌细胞的增殖和迁移。此外,hnRNPA2B1还促进宫颈癌细胞的有氧糖酵解,包括乳酸分泌、葡萄糖摄取、ATP产生、细胞外酸化率(ECAR)和耗氧率(OCR)。 m6A 位点发现 LDHA 是 hnRNPA2B1 的下游靶标。此外,hnRNPA2B1通过m6A依赖性方式增强LDHA mRNA的稳定性。 LDHA抑制剂(FX-11)可以逆转hnRNPA2B1的作用。综上所述,数据显示hnRNPA2B1通过m6A/LDHA依赖的方式促进宫颈癌细胞的增殖、迁移和有氧糖酵解。这些发现可能会为宫颈癌治疗带来新思路。© 2024。作者获得 Springer Science Business Media, LLC(Springer Nature 旗下公司)的独家许可。
N6-methyladenosine (m6A) modification is, a more common epigenetic modification, mainly found in mRNA. More and more researches have shown the important functions of m6A on human cancers. This study seeks to explore the role of hnRNPA2B1 and m6A-dependent mechanism in cervical cancer. Elevated hnRNPA2B1 indicated the poor prognosis of cervical cancer patients. Enforced hnRNPA2B1 reduced the apoptosis, and accelerated the proliferation and migration of cervical cancer cells in vitro. Besides, hnRNPA2B1 promoted the aerobic glycolysis of cervical cancer cells, including the lactate secretion, glucose uptake, ATP production, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). LDHA was found as the downstream target of hnRNPA2B1 by m6A site. Moreover, hnRNPA2B1 enhanced the mRNA stability of LDHA through m6A-dependent manner. LDHA inhibitor (FX-11) could reverse the effect of hnRNPA2B1. Taken together, the data revealed that hnRNPA2B1 promoted the proliferation, migration and aerobic glycolysis of cervical cancer cells by m6A/LDHA-dependent manner. These findings might bring a new idea for cervical cancer treatment.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.