结直肠癌（CRC）是我国高发的恶性肿瘤之一。膳食纤维通过菌群酵解产生的丁酸盐可降低CRC的发生风险，但是具体机制尚不明确。我们通过转录组测序发现丁酸钠可抑制c-Myc信号通路并上调一个未知功能的lncRNA LOH12CR2的表达。通过临床样本检测分析发现LOH12CR2在CRC组织中表达降低。ChiRP结果发现LOH12CR2可结合m6A甲基化转移酶METTL14，并降低c-Myc mRNA稳定性。由此我们提出丁酸钠通过表观遗传上调LOH12CR2表达，LOH12CR2通过结合METTL14促进c-Myc mRNA的m6A甲基化降低其稳定性，从而发挥抗肿瘤作用的假说。我们拟从临床样本，小鼠实验，细胞模型三个层面利用ChIP，MeRIP，m6A测序等技术验证此假设。研究结果将有助于揭示LOH12CR2在丁酸钠抗肿瘤中的作用及机制，同时也为研究膳食纤维对CRC的预防作用提供实验和理论依据。

Colorectal cancer (CRC) is one of the most common gastrointestinal tumors in China. Scientific studies suggest that the risk of colorectal cancer is suppressed by dietary fiber, which have a potent tumor-suppressive effect by butyrate-dependent manner. However, the molecular mechanism underlying butyrate anti-tumor activity is still unclear. Our preliminary data showed that sodium butyrate (NaB) down-regulated the expression of c-Myc and inhibited the c-Myc signal pathway. The results from RNA sequencing showed NaB could up-regulate the expression of LOH12CR2, an unknown lncRNA. The analysis from clinical CRC tissues indicated the expression of LOH12CR2 is lower in CRC tissue than that in normal tissues. The data from ChiRP demonstrated that LOH12CR2 could bind METTL14 and decrease the stability of c-Myc mRNA。We propose that NaB epigenetic up-regulate the LOH12CR2, which induces the m6A methylation c-Myc mRNA by binding METTL14, further accelerates the degradation of c-Myc mRNA to prevent tumorigenesis. We will test this hypothesis in clinical samples, xenograft tumor in nude mice and CRC cell line by using methods of ChIP, MeRIP, m6A-Seq etc. Results from this study will be helpful to clarify the molecular mechanism of action of LOH12CR2 and NaB in CRC prevention, thus will provide experimental and theoretical basis for the application of dietary fiber in prevention of CRC.