ENST00000428100通过MACC1调节mTOR通路影响结肠癌干细胞代谢可塑性的机制研究

肿瘤细胞存在代谢异常。肿瘤干细胞具有自我更新能力，是肿瘤复发转移的关键因素。那么结肠癌干细胞的代谢模式是以Warburg效应为主，还是以线粒体氧化磷酸化为主，目前尚不清楚。前期发现，非编码RNA ENST00000428100（lncRNA）参与结肠癌干细胞形成和糖酵解，并调控MACC1和mTOR通路。基于MACC1和mTOR通路均参与肿瘤细胞糖酵解，本项目拟探讨lncRNA通过MACC1调节mTOR通路影响结肠癌干细胞代谢可塑性的机制。首先，明确结肠癌干细胞的能量代谢模式；其次，阐明lncRNA与MACC1对结肠癌干细胞能量代谢方式及其代谢可塑性的调节；再次，明确两分子间的调控方式，和对mTOR通路的作用；最后，明确上述分子在肿瘤组织中表达的临床意义。本研究旨在阐明以lncRNA-MACC1-mTOR为核心的结肠癌肿瘤干细胞代谢可塑性调控方式，并为肿瘤诊疗提供新的策略，及可能的干预措施。

Dysfuntional cellular metabolism exists in tumor cells. Cancer stem cells (CSC) have ability of self-renewal, which plays a critical role in tumor recurrence and metastasis. However, the metabolic pattern of colorectal CSC is largely unknown. Whether it is mainly based on the Warburg effect, or mitochondrial oxidative phosphorylation (OXPHOS) needs to be elucidated. Our previous study suggested that ENST00000428100, a long noncoding RNA (lncRNA), was involved in the sphere formation of colorectal CSC and glycolysis. Moreover, ENST00000428100 regulated the level of MACC1 and mTOR signaling pathway. Given that both MACC1 and mTOR pathway participated in glycolysis, this study will clarify the mechanism of ENST00000428100 regulating mTOR signaling pathway by MACC1 and determine the metabolic plasticity of colorectal CSC. First, we decide to demonstrate the metabolic pattern of colorectal CSC. Second, we want to detect the effects of ENST00000428100 and MACC1 on the metabolic pattern and plasticity of colorectal CSC. Third, we decide to understand the regulation between ENST00000428100 and MACC1, as well as their modulation of mTOR signaling pathway. Finally, we want to demonstrate the expression levels of ENST00000428100 and MACC1 in colorectal cancers, as well as their clinical significance. The purpose of this study was to clarify the regulation of metabolic plasticity in colorectal CSC, and the underlying mechanism of ENST00000428100-MACC1-mTOR network. Our study will provide new potential strategies for cancer diagnosis and treatment.