LncRNA-91H作为新的结直肠癌血清标志物及其调控机制研究

Long non-coding RNA (lncRNA) can regulate the expression of its encoding genes by a variety of ways which is involved in the occurrence and development of many diseases including cancers. The insulin-like growth factor 2 (IGF2) which can promote proliferation, migration and metastasis of tumor cell is highly expressed in colorectal cancer (CRC). Our previous studies have shown that the expression of lncRNA-91H was high in the colorectal cancer (CRC) patients' sera and tumor tissues, which was closely related to the abnormally high expression of IGF2, but the mechanism of lncRNA-91H how to regulate the expression of IGF2 is not yet clear. On the basis of preliminary research, we intend to explore the effects and mechanism of 91H in the regulation of IGF2 expression in CRC, and investigate the role of 91H on the occurrence and development of CRC, and then explore the role of 91H in serum as a new biomarker in the early diagnosis, disease condition analysis, curative effect evaluation and prognosis of CRC, providing new ideas for the study of the pathogenesis and new targets for clinical diagnosis of CRC.

长链非编码RNA（lncRNA）可通过多种方式调控编码基因的表达，参与包括肿瘤在内的多种疾病的发生发展。胰岛素样生长因子2（IGF2）在结直肠癌（CRC）肿瘤组织中高表达，能促进肿瘤细胞的增殖、迁徙及转移。我们前期研究表明，lncRNA-91H在结直肠癌（CRC）患者癌组织及血清中均呈高表达，且与IGF2的异常高表达密切相关，但lncRNA-91H是如何调控IGF2的表达机制目前仍未明确。本项目拟在前期研究的基础上，探讨CRC中91H对IGF2表达的调控作用及其机制，以深入研究91H在CRC发生发展中的作用，并探讨血清91H 作为新的标志物在CRC早期诊断、病情分析、疗效评估和预后判断中的价值，以期为CRC的发病机制研究及临床诊断提供新的思路和新的靶标。

长链非编码RNA（lncRNA）可通过多种方式调控编码基因的表达，参与包括肿瘤在内的多种疾病的发生发展。胰岛素样生长因子2（IGF2）在结直肠癌（CRC）肿瘤组织中高表达，能促进肿瘤细胞的增殖、迁徙及转移。我们前期研究表明，lncRNA-91H在结直肠癌（CRC）患者癌组织及血清中均呈高表达，且与IGF2的异常高表达密切相关，但lncRNA-91H是如何调控IGF2的表达机制目前仍未明确。本项目在前期研究的基础上，首先构建及鉴定了91H干扰载体，体内外试验证实lncRNA 91H在CRC细胞增殖、侵袭转移及凋亡过程中发挥着重要作用，随后采用RNA结合蛋白免疫沉淀(RIP)，蛋白质谱分析以及RNA pull down技术分析发现lncRNA 91H可通过与IGF2BP2蛋白结合，显著促进CRC IGF2蛋白表达。最后，我们通过收集临床CRC患者、良性病变患者与健康体检患者血清，初步构建了体外血清lncRNA-91H检测方法，并完成了方法学与临床验证。结果表明，lncRNA 91H在结直肠患者血清内具有显著高表达的特异性，其表达与患者肿瘤复发转移以及总生存期密切相关（P<0.05）。此外，我们通过透射电镜以及免疫印迹试验发现lncRNA 91H主要以外泌体形式存在于CRC患者外周血中。综上，本次研究系统论证了lncRNA 91H可通过调控IGF2表达促进CRC发生发展，外周血外泌体内lncRNA 91H可作为潜在的新的肿瘤标志物用于CRC复发转移以及总生存率预测。