研究动态
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TRMT10C 介导的 circFAM126A m7G 修饰通过调节细胞糖酵解抑制肺癌生长。

TRMT10C-mediated m7G modification of circFAM126A inhibits lung cancer growth by regulating cellular glycolysis.

发表日期:2024 Sep 18
作者: Qingyun Zhao, Xiaofei Li, Jiaxi Wu, Ruirui Zhang, Sixian Chen, Dunyu Cai, Haotian Xu, Wenyi Peng, Gang Li, Aruo Nan
来源: CELL BIOLOGY AND TOXICOLOGY

摘要:

N7-甲基鸟苷 (m7G) 修饰和环状 RNA (circRNA) 已被证明在肺癌的发生发展中发挥重要作用。然而,circRNA的m7G修饰尚未完全阐明。这项研究揭示了 circFAM126A 中存在 m7G 修饰。我们提出了新的假设,即甲基转移酶 TRMT10C 介导 circFAM126A 的 m7G 修饰,并且 m7G 修饰的 circFAM126A 的稳定性降低。 circFAM126A 在肺癌中下调,并在体外和体内显着抑制肺癌生长。 circFAM126A的表达与肺癌的分期和肿瘤直径相关,circFAM126A可作为肺癌的潜在分子靶点。 circFAM126A 增加 HSP90 泛素化并抑制 AKT1 表达以调节细胞糖酵解,最终抑制肺癌进展的分子机制已被阐明。该研究不仅拓宽了有关circRNA表达和调控模式的知识,而且从表观遗传学的角度为调节肿瘤细胞代谢和影响肿瘤细胞命运的分子机制提供了新的见解。这些发现将有助于制定肺癌预防和治疗的新策略。© 2024。作者。
The N7-methylguanosine (m7G) modification and circular RNAs (circRNAs) have been shown to play important roles in the development of lung cancer. However, the m7G modification of circRNAs has not been fully elucidated. This study revealed the presence of the m7G modification in circFAM126A. We propose the novel hypothesis that the methyltransferase TRMT10C mediates the m7G modification of circFAM126A and that the stability of m7G-modified circFAM126A is reduced. circFAM126A is downregulated in lung cancer and significantly inhibits lung cancer growth both in vitro and in vivo. The expression of circFAM126A correlates with the stage of lung cancer and with the tumour diameter, and circFAM126A can be used as a potential molecular target for lung cancer. The molecular mechanism by which circFAM126A increases HSP90 ubiquitination and suppresses AKT1 expression to regulate cellular glycolysis, ultimately inhibiting the progression of lung cancer, is elucidated. This study not only broadens the knowledge regarding the expression and regulatory mode of circRNAs but also provides new insights into the molecular mechanisms that regulate tumour cell metabolism and affect tumour cell fate from an epigenetic perspective. These findings will facilitate the development of new strategies for lung cancer prevention and treatment.© 2024. The Author(s).