LINC02167通过与KSR1 mRNA m5C修饰位点结合调控其稳定性促进结直肠癌转移的作用及机制研究

复发转移是影响结直肠癌（CRC）患者生存预后的关键因素。LncRNA与RNA m5C修饰在CRC转移中的作用及机制尚不清楚。课题组预实验发现一个新的LncRNA LINC02167能够促进CRC转移，MYC在转录水平促进其高表达；KSR1作为Ras/Raf/MAPK通路关键基因， LINC02167通过招募YBX1及ILF3与KSR1 mRNA的 m5C位点结合并维持其稳定性。据此提出科学假说：MYC介导的LINC02167通过KSR1/Ras/Raf/MAPK通路促进CRC转移。本项目拟在细胞、动物及人体组织水平对上述假说进行深入研究，利用RNA Bis Seq、MeRIP、RNA-Pulldown等技术，重点探索LINC02167在CRC中表达增高及其通过m5C修饰调控KSR1 mRNA稳定性的分子机制。本研究将丰富CRC转移的分子机制，为探寻CRC新的治疗靶标提供科学理论依据。

Recurrence and metastasis are the key factors affecting the survival and prognosis of patients with colorectal cancer (CRC). The role and mechanism of LncRNA and RNA m5C modification in CRC metastasis are still unknown. Our preliminary data found that a new LncRNA LINC02167 can promote CRC metastasis and MYC can meditate its high expression in CRC at the transcription level; KSR1 acts as a key gene of the Ras / Raf / MAPK pathway, LINC02167 can recruit YBX1 and ILF3 to bind to the m5C site of KSR1 mRNA and maintains its stability. Based on these working, a scientific hypothesis is proposed: MYC-mediated LINC02167 promotes CRC metastasis through the KSR1 / Ras / Raf / MAPK pathway. This project intends to conduct research on the above hypotheses at the level of cell, animal, and human tissues. Using technologies such as RNA Bis Seq, MeRIP, and RNA-Pulldown, we will focus on exploring the molecular mechanism about overexpression of LINC02167 in CRC and its role in regulating KSR1 mRNA stability by m5C modification. This study will enrich the molecular mechanism of CRC metastasis and provide a theoretical basis for exploring new therapeutic targets for CRC.