转移
癌症研究
生物
细胞生长
巨噬细胞极化
结直肠癌
细胞迁移
M2巨噬细胞
细胞培养
肿瘤微环境
癌症
巨噬细胞
体外
生物化学
遗传学
肿瘤细胞
作者
Junfei Gu,Ruolan Sun,Decai Tang,Fuyan Liu,Xiangwei Chang,Qiaohan Wang
标识
DOI:10.1007/s10565-021-09679-w
摘要
Colorectal cancer (CRC) is regarded as one of the commonest cancer types around the world. Due to the poor understanding on the causes of CRC formation and progression, this study sets out to investigate the physiological mechanisms by which Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (ARCR) regulates CRC growth and metastasis, and the role in which M2 macrophage polarization plays in this process. An orthotopic-transplant model of CRC was established to evaluate the influence of ARCR on the polarization of M2 macrophage and the growth and metastasis of tumors. Next, the binding affinity among Sp1, ZFAS1, miR-153-5p, and CCR5 was identified using multiple assays. Finally, after co-culture of bone marrow–derived macrophages (BMDM) with CRC cell line CT26.WT, the cell proliferative, invasive, and migrated abilities were assessed in gain- or loss-of-function experiments. ARCR inhibited the infiltration of M2 macrophages into tumor microenvironment to suppress the CRC growth and metastasis in vivo. Additionally, ARCR inhibited the transcription of ZFAS1 by reducing Sp1 expression to repress M2 macrophage polarization. Moreover, ZFAS1 competitively binds to miR-153-3p to upregulate the CCR5 expression. Finally, ARCR suppressed the polarization of M2 macrophages to inhibit the tumor growth and tumor metastasis in CRC by mediating the Sp1/ZFAS1/miR-153-3p/CCR5 regulatory axis. Collectively, ARCR appears to suppress the CRC cell growth and metastasis by suppressing M2 macrophage polarization via Sp1/ZFAS1/miR-153-3p/CCR5 regulatory axis.Graphical abstract1. ARCR suppress the CRC cell growth and metastasis2. ZFAS1 promotes CCR5 expression by competitively binding to miR-153-3p.3. Sp1 promotes M2 macrophage polarization by activating ZFAS1 via miR-153-3p/CCR5.4. The study unveiled a protective target against CRC.
科研通智能强力驱动
Strongly Powered by AbleSci AI