长链非编码RNA CTD-2339L15.1作为ceRNA在胰腺癌中的作用及机制

Recent studies have confirmed that lncRNA can competitively bind with miRNA by acting as a competing endogenous RNA and upregulate the expression of miRNA target genes. Our previous study found that CTD-2339L15.1 is significantly upregulated and plays an oncogenic role in pancreatic cancer; CTD-2339L15.1 was negatively correlated with the expression of miR-29a-3p and positively correlated with the expression of MUC1 and KIAA0101; Bioinformatics analysis showed that CTD-2339L15.1 and MUC1/KIAA0101 mRNA competitively bind with miR-29a-3p. Therefore, we assume that CTD-2339L15.1 can regulate the expression of MUC1 and KIAA0101 by competitively binding with miR-29a-3p, which can promote the development of pancreatic cancer. This study intends to analyze the correlation between CTD-2339L15.1 and the clinical features and prognosis of pancreatic cancer, and explore the role and molecular mechanism of CTD-2339L15.1 in the development and progression of pancreatic cancer by using in vitro and in vivo functional experiments, RIP and dual luciferase reporter gene system; which will improve the understanding of the pathogenesis of this disease and provide new ideas and new targets for the diagnosis and treatment of pancreatic cancer.

新近研究证实lncRNA可作为ceRNA竞争性结合miRNA，从而上调miRNA靶基因的表达。我们前期研究发现，胰腺癌组织中CTD-2339L15.1显著上调，并且在胰腺癌中起着癌基因的作用；CTD-2339L15.1与miR-29a-3p表达成负相关，与MUC1和KIAA0101表达成正相关；生物信息分析提示CTD-2339L15.1与MUC1以及KIAA0101 mRNA均可结合miR-29a-3p。由此，我们设想CTD-2339L15.1通过竞争性结合miR-29a-3p调控MUC1以及KIAA0101 表达，从而促进胰腺癌发生发展。本项目拟分析CTD-2339L15.1与胰腺癌临床特征及预后相关性，利用体内外功能实验、RIP、双荧光素酶报告基因系统等手段明确CTD-2339L15.1在胰腺癌发生发展的作用及分子机制，完善对该疾病发病机制的认识，为胰腺癌的诊治提供新思路和新靶点。

背景：长链非编码RNA在胰腺导管腺癌（PDAC）的发生发展中起着重要作用。LncRNA TPT1-AS1是一常见的非编码RNA，其在PDAC中的作用及其机制尚不清楚。.方法：首先，通过生存分析和定量PCR检测lncRNA-TPT1-AS1在PDAC标本和细胞系中的表达及其对预后的影响。用CCK8、Edu、集落形成、Transwell法和划痕法测定细胞增殖、迁移和侵袭能力。采用原位肿瘤模型检测肿瘤生长和转移情况。.结果：低分化胰腺癌及晚期胰腺癌中lncRNA-TPT1-AS1高表达，且lncRNA-TPT1-AS1高表达与预后不良相关。我们通过TPT1-AS1的过表达和敲除实验证明，TPT1-AS1在体内外均能促进PDAC细胞的增殖、迁移、侵袭和EMT进展。过表达和敲除实验证实miR-30a-5p抑制PDAC细胞的增殖、迁移、侵袭和EMT进程，并介导TPT1-AS1的生物学效应。此外，我们还证明了ITGB3是miR-30a-5p的直接靶点，并且ITGB3促进PDAC细胞的增殖、迁移、侵袭和EMT进展。.结论：TPT1-AS1竞争性结合miR-30a-5p进而调控ITGB3表达，促进胰腺癌的增殖和转移，为胰腺癌早期诊断及寻找有效的治疗靶点提供崭新的思路。