长链非编码RNA（lncRNA）在肿瘤发生发展中发挥极其重要作用，但绝大部分lncRNA的功能尚不清楚。申请者利用基因芯片筛选发现一个新的lncRNA参与结直肠癌发生发展，其功能及作用未见报道。进一步研究发现lncRNA SH3PXD2A-AS1在结直肠癌组织中高表达，且促进结直肠癌细胞生长及体内转移。RNA-Pull down实验及蛋白质谱鉴定发现SH3PXD2A-AS1可能通过与TCF1蛋白结合发挥调控作用，但两者相互作用的机制尚不清楚。据此提出科学假说：SH3PXD2A-AS1可能通过与TCF1结合调控Wnt/β-catenin信号通路，从而促进结直肠癌细胞的生长及体内转移。本项目拟利用我们构建的多种细胞、动物和人群模型研究SH3PXD2A-AS1通过TCF1/Wnt/β-catenin通路调控结直肠癌生长和转移的分子机制。本项目的成功将为结直肠癌的基因治疗和分子诊断提供新靶点。

The long noncoding RNA (lncRNA) plays a crucial role in tumorigenesis, but the functions of most lncRNAs are still unknown. We found that a new lncRNA was closely related to colorectal cancer (CRC) development by gene chip, but little is known about its function. Our recent data showed that lncRNA-SH3PXD2A-AS1 is overexpressed in CRC tissues, and promote CRC cell growth and metastasis in vivo. RNA-Pull down and mass spectrometry results showed that SH3PXD2A-AS1 may bind to TCF1 protein, but the molecular mechanism is not clear. On the basis of these findings, we propose the hypothesis that SH3PXD2A-AS1 may promote CRC cell growth and metastasis by regulating TCF1/Wnt/β-catenin signaling pathway. This project intends to study the mechanism that SH3PXD2A-AS1 regulates CRC growth and metastasis via a variety of cell and animal models we constructed. The accomplishment of this project will provide a new potential target for CRC treatment.