NCAPG-PRDX2轴调控结肠癌干细胞自我更新与耐药的作用机制研究

Cancer stem cells and drug resistance play a key role in colorectal cancer recurrence and metastasis, but the mechanism is not yet clear. Applicants confirmed in previous work that PRDX2 is involved in the maintenance of colon cancer stem cell function and is involved in the promotion of drug resistance in colon cancer cells. Through biological information analysis, NCAPG is highly expressed in colon cancer, which is correlated with the prognosis of colon cancer. The expression of NCAPG in colon cancer cell microspheres and MTX-resistant cells is significantly lower than that of colon cancer cells. It could be concluded that NCAPG may be involved in the regulation of colon cancer stem cell self-renewal and drug resistance. The correlation between NCAPG and PRDX2 expression in colon cancer is high, suggesting that NCAPG may interact with PRDX2 to participate in the functional regulation of colon cancer stem cells. This topic intends to further investigate the regulatory role of NCAPG-PRDX2 axis in colon cancer stem cells and the interaction between NCAPG and PRDX2 at the four levels of tissues, animals, cells and molecules.

结肠癌术后复发转移中，肿瘤干细胞和耐药发挥了关键作用，其中的机制尚未明确。申请者在前期工作中证实了PRDX2参与维持结肠癌干细胞功能，并促进结肠癌细胞耐药。根据生物学信息数据分析结果，NCAPG在结肠癌中过表达，与结肠癌预后相关，NCAPG在结肠癌干细胞微球体和甲氨蝶呤耐药细胞中表达显著低于对照组结肠癌细胞，提示NCAPG可能参与调控结肠癌干细胞自我更新及耐药。在结肠癌中NCAPG与PRDX2表达相关性高，提示NCAPG可能与PRDX2相互作用，共同参与结肠癌干细胞功能调节。本课题拟进一步在组织、动物、细胞、分子四个层面深入探讨NCAPG-PRDX2对结肠癌干细胞自我更新及耐药的调控作用以及NCAPG与PRDX2之间的相互作用机制。

结肠癌术后复发转移中，肿瘤干细胞和耐药发挥了关键作用，其中的机制尚未明确。申请者在前期工作中证实了PRDX2参与维持结肠癌干细胞功能，并促进结肠癌细胞耐药。结合生物学信息数据分析结果，课题组临床大样本数据、细胞和动物水平、分子机制验证三个层面层层深入验证了在结肠癌中NCAPG与干细胞自我更新能力相关联，抑制NCAPG表达能够减弱肿瘤干细胞自我更新能力，而且进一步证实NCAPG通过与PRDX2相互作用共同参与调控结肠癌干细胞自我更新能力的调节。