Sohlh2在结肠癌干细胞介导的肿瘤复发和转移中作用的实验研究

Colon cancer is the most common gastrointestinal malignancy, the recurrence and metastasis after surgery is the main cause of death. Cancer stem cells (CSCs) are the small amounts of cancer cells found within tumors, which possess self-renewal and multidifferentiation potential characteristics similar to normal stem cells. CSCs are the source of tumor recurrence and metastasis. Sohlh2 belongs to the bhlh transcription factor family. Our preliminary studies have confirmed sohlh2 is a noval tumor suppressor, which inhibits colon cancer cell proliferation, migration and invasion. In this project, we are going to perform the methods of gene transfection and RNA interference to investigate the functions of sohlh2 during the process of colon cancer stem cell proliferation ,migration, invasion, as well as tumorigenesis and matastasis in vivo. With the methods of gene chips, co-immunoprecipitation(CO-IP) and luciferase reporting system, the effects of sohlh2 on Wnt/β-catenin signaling pathway will be detected, especially for the regulation of sohlh2 on Wnt/β-catenin signaling pathway activated by an important inflammatory factor, PGE2. This study may help us to reveal the signaling pathway of colon cancer recurrence and metastasis, and provide novel diagnotic and therapeutic targets of colon cancer recurrence and metastasis.

结肠癌是胃肠道最常见的恶性肿瘤,术后复发和转移是其致死的主要原因。肿瘤干细胞（CSCs）是肿瘤组织中存在的具有类似干细胞自我更新和分化潜能特性的少量肿瘤细胞，是肿瘤复发转移的根源。Sohlh2是bhlh家族的转录因子，我们的前期研究已证实，sohlh2是一个新抑癌基因，可抑制结肠癌细胞的增殖、迁移和侵袭。本项目将利用基因转染和RNA干扰等技术，检测sohlh2在结肠癌干细胞增殖、侵袭迁移、肿瘤发生和转移中的作用；通过基因芯片、CO-IP和Luciferase报告系统等，检测sohlh2对结肠癌干细胞Wnt/β-catenin信号通路的调控，尤其探讨sohlh2对炎性因子PGE2激活Wnt/β-catenin信号通路的影响。本研究将为揭示结肠癌复发转移的信号通路，以及结肠癌复发转移的早期基因诊断和治疗提供新理论基础和新靶点。

结肠癌是胃肠道最常见的恶性肿瘤,术后复发和转移是其致死的主要原因。肿瘤干细胞（CSCs）是肿瘤组织中存在的具有类似干细胞自我更新和分化潜能特性的少量肿瘤细胞，是肿瘤复发转移的根源。Sohlh2是bhlh家族的转录因子，我们的前期研究已证实，sohlh2是一个新抑癌基因，可抑制结肠癌细胞的增殖、迁移和侵袭。本项目将利用基因转染和RNA干扰等技术，检测sohlh2在结肠癌干细胞增殖、侵袭迁移、肿瘤发生和转移中的作用；通过基因芯片、CO-IP和Luciferase报告系统等，检测sohlh2对结肠癌干细胞Wnt/β-catenin信号通路的调控，结果发现：sohlh2可以通过下调LncRNA-H19转录来抑制β-catenin及其下游信号通路，从而抑制结肠癌干细胞的扩增，促进其分化，从而减弱其干性，不利于其干性维持。本研究可为揭示结肠癌复发和转移的信号通路，以及结肠癌复发和转移的早期基因诊断和治疗提供新的理论基础和新的靶点。