N6-methyladenosine-modified circRPS6KC1 regulated cellular senescence in prostate cancer via FOXM1/PCNA axis

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2024-11-15 DOI:10.1016/j.cellsig.2024.111510

Xuan Shu , Jiahe Yi , Jiangfeng Li , Yufan Ying , Yijie Tang , Ziyan Chen , Jiaming Wang , Fenghao Zhang , Dingheng Lu , Yuqing Wu , Jiazhu Sun , Shen Lin , Zhixiang Qi , Danni Chen , Xiao Wang , Hong Chen , Liping Xie , Xueyou Ma , Jindan Luo

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引用次数: 0

Abstract

Prostate cancer (PCa) gradually becomes the most common cancer in men in many countries, of which circRNAs and methylated modification exert an essential role in PCa progression. However, the concrete mechanisms of N6-methyladenosine (m6A) modification of circRNAs in PCa remain unclear. In our study, we identified circRPS6KC1, a novel and up-regulated circular RNA in PCa, through circRNA sequencing. We discovered that METTL3 and YTHDF1 were involved in the m6A modification of circRPS6KC1 and the stabilization. Furthermore, we found that suppression of circRPS6KC1 contributed to cellular senescence in prostate cancer. CircRPS6KC1 acted as the miR-761 sponge to regulate the FOXM1 expression. FOXM1 mediated the transcription of PCNA and influenced the p21 degradation, which resulted in up-regulation of p21 protein in a p53-independent manner. In conclusion, our findings showed that N6-methyladenosine modification by METTL3 and YTHDF1 stabilized circRPS6KC1, and circRPS6KC1 played an essential role on cellular senescence via FOXM1/PCNA axis in prostate cancer.

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N6-甲基腺苷修饰的 circRPS6KC1 通过 FOXM1/PCNA 轴调控前列腺癌的细胞衰老。

在许多国家，前列腺癌（PCa）逐渐成为男性最常见的癌症，其中循环RNA和甲基化修饰在PCa的进展中发挥着至关重要的作用。然而，PCa 中 circRNAs 的 N6-甲基腺苷（m6A）修饰的具体机制仍不清楚。在我们的研究中，我们通过circRNA测序发现了circRPS6KC1，它是PCa中一种新的、上调的环状RNA。我们发现METTL3和YTHDF1参与了circRPS6KC1的m6A修饰和稳定。此外，我们还发现，抑制 circRPS6KC1 会导致前列腺癌细胞衰老。circRPS6KC1作为miR-761海绵调节FOXM1的表达。FOXM1 介导 PCNA 的转录并影响 p21 的降解，从而导致 p21 蛋白以 p53 无关的方式上调。总之，我们的研究结果表明，METTL3和YTHDF1的N6-甲基腺苷修饰稳定了circRPS6KC1，circRPS6KC1通过FOXM1/PCNA轴在前列腺癌的细胞衰老中发挥了重要作用。

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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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.