胰腺癌是恶性程度高、预后极差的消化道常见恶性肿瘤。证据显示胰腺癌高复发率及放化疗不敏感与肿瘤干细胞密切相关。我们前期研究发现，IGF2BP2在胰腺癌中高表达，且与预后不良正相关；IGF2BP2结合LncRNA DANCR而调控其表达，促进胰腺癌干细胞特性；RNA共沉淀证实DANCR直接结合干细胞基因Lin28B。因此我们提出“IGF2BP2-DANCR-Lin28B信号轴促进胰腺癌干细胞特性”的假设。为了证实该假设，本课题拟研究：1、IGF2BP2如何结合并稳定DANCR表达；2、IGF2BP2-DANCR是否通过以下机制调控Lin28B：①DANCR结合Lin28B增强其下游转录活性；②DANCR通过ceRNA功能促进Lin28B表达；3、IGF2BP2,DANCR,Lin28B在胰腺癌中的临床生物学意义。本项目为阐明胰腺癌干细胞特性维持的分子机制及关键环节、研发靶向药物提供科学依据。

Pancreatic cancer is a common tumor of gastrointestinal system with high degree of malignance and poor prognosis. There is evidence that high recurrence and drug resistance of pancreatic cancer is closely related with cancer stem cell. Our previous study indicated that IGF2BP2 was an independent prognostic marker in pancreatic cancer. IGF2BP2 could regulate the expression of LncRNA DANCR through binding with it, which increased the stemness feature of pancreatic cancer. The DANCR could directly bind with Lin28B using RNA-pulldown. Therefore, we give the hypothesis that IGF2BP2-DANCR-Lin28B axis increases the stemness features of pancreatic cancer. To test this hypothesis, several experiments were carried out as following: (1) How IGF2BP2 stabilizes DANCR through binding to it? (2) The mechanism of IGF2BP2-DANCR regulating Lin28B: ① DANCR binding with Lin28B increases the transcription activity of Lin28B; ② DANCR up-regulates Lin28B through ceRNA function. (3) The clinical significance of IGF2BP2-DANCR-Lin28B axis. The aim of this project is to clarifies the molecular mechanism and signal pathway of pancreatic cancer stem cell maintenance, in order to provide further scientific basis for targeting therapy of pancreatic cancer.