LOH12CR2 activated by sodium butyrate suppresses tumorigenesis in colorectal cancer via METTL14-mediated N6-methyladenosine modification of SPC24 mRNA

IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Yanbing Lin , Qianwen Zhou , Mengqi Li , Sucheng Hou , Jia Xu , Dongfang Dai , Xiaoqin Yuan
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引用次数: 0

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Epidemiological studies suggest that dietary fiber intake reduces CRC risk, with butyrate, a fermentation product of dietary fiber, showing promising anti-cancer properties. However, the underlying molecular mechanisms remain poorly understood. In this study, we reveal that sodium butyrate (NaB) upregulates the long non-coding RNA LOH12CR2 in CRC cells, which is crucial for NaB's anti-tumor effects both in vitro and in vivo. Our transcriptome sequencing and subsequent functional analyses demonstrate that LOH12CR2 mediates NaB’s impact by inhibiting the mitotic regulator SPC24, which is overexpressed in CRC. Mechanistically, LOH12CR2 interacts with and stabilizes the m6A methyltransferase METTL14, enhancing m6A modification and subsequent degradation of SPC24 mRNA. We identify a novel LOH12CR2-METTL14-m6A regulatory axis in CRC, through which NaB exerts its anti-tumor effects by downregulating SPC24 post-transcriptionally, thereby suppressing tumor growth and progression. Our findings elucidate a new molecular pathway through which dietary fiber protects against CRC and highlight LOH12CR2 as a potential therapeutic target.
丁酸钠激活的LOH12CR2通过mettl14介导的n6 -甲基腺苷修饰SPC24 mRNA抑制结直肠癌的肿瘤发生
结直肠癌(CRC)是全球癌症相关死亡的主要原因。流行病学研究表明,膳食纤维摄入可降低结直肠癌风险,其中膳食纤维发酵产物丁酸盐显示出良好的抗癌特性。然而,潜在的分子机制仍然知之甚少。在本研究中,我们发现丁酸钠(NaB)在CRC细胞中上调长链非编码RNA LOH12CR2,这是NaB在体外和体内抗肿瘤作用的关键。我们的转录组测序和随后的功能分析表明,LOH12CR2通过抑制有丝分裂调节因子SPC24介导NaB的影响,SPC24在CRC中过表达。在机制上,LOH12CR2与m6A甲基转移酶METTL14相互作用并稳定m6A甲基转移酶,增强m6A修饰和随后的SPC24 mRNA降解。我们在CRC中发现了一个新的LOH12CR2-METTL14-m6A调控轴,NaB通过该调控轴转录后下调SPC24来发挥其抗肿瘤作用,从而抑制肿瘤的生长和进展。我们的研究结果阐明了膳食纤维预防结直肠癌的一个新的分子途径,并强调了LOH12CR2是一个潜在的治疗靶点。
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
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.
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