N⁶-methyladenosine (m⁶A) reader HNRNPA2B1 accelerates the cervical cancer cells aerobic glycolysis.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-10-19 DOI:10.1007/s10863-024-10042-x

Mengke Wen, Na Yi, Bulabiyamu Mijiti, Shihong Zhao, Guqun Shen

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Abstract

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.

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N6-甲基腺苷（m6A）阅读器 HNRNPA2B1 可加速宫颈癌细胞的有氧糖酵解。

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 对人类癌症具有重要作用。本研究旨在探讨 hnRNPA2B1 在宫颈癌中的作用及 m6A 依赖性机制。hnRNPA2B1 的升高表明宫颈癌患者的预后较差。强化的 hnRNPA2B1 会减少宫颈癌细胞的凋亡，并加速其体外增殖和迁移。此外，hnRNPA2B1还能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）和耗氧量（OCR）。通过 m6A 位点发现 LDHA 是 hnRNPA2B1 的下游靶点。此外，hnRNPA2B1通过m6A依赖性方式增强了LDHA的mRNA稳定性。LDHA抑制剂（FX-11）可以逆转hnRNPA2B1的作用。综上所述，这些数据揭示了 hnRNPA2B1 通过 m6A/LDHA 依赖性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的治疗带来新的思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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