LINC00543通过促进上皮-间质转化和诱导肿瘤相关巨噬细胞M2极化来促进结直肠癌的转移。
LINC00543 promotes colorectal cancer metastasis by driving EMT and inducing the M2 polarization of tumor associated macrophages.
发表日期:2023 Feb 25
作者:
Jinsen Zheng, Rongzhang Dou, Xinyao Zhang, Bo Zhong, Chenggang Fang, Qian Xu, Ziyang Di, Sihao Huang, Zaihuan Lin, Jialin Song, Shuyi Wang, Bin Xiong
来源:
Journal of Translational Medicine
摘要:
肿瘤微环境(TME)与癌细胞的相互作用已成为大肠癌(CRC)转移的关键因素。少量经历上皮-间充质转化(EMT)的CRC细胞通过调节各种细胞成分,促进了TME的重塑。通过免疫组织化学分析、RNA免疫共沉淀(RIP)、RNA反义纯化(RAP)、双荧光素酶检测等方法研究LINC00543在CRC中的生物功能和调控。采用一系列体内外实验阐明了LINC00543在CRC转移中的作用。我们发现,长链非编码RNA LINC00543在结肠直肠癌组织中高表达,与CRC患者TNM分期进展和预后不良相关。LINC00543的过表达通过增强EMT和重塑TME促进了CRC细胞的肿瘤发生和转移。机制上,LINC00543阻止了pre-miR-506-3p跨越核-质转运蛋白XPO5的运输,从而减少成熟miR-506-3p的产生,导致FOXQ1表达增加并诱导EMT。此外,FOXQ1上调诱导CCL2表达,加速了巨噬细胞的招募和M2极化。我们的研究表明,LINC00543通过pre-miR-506-3p/FOXQ1轴增强了CRC细胞的EMT,导致CCL2增高,招募和M2极化巨噬细胞,从而刺激CRC的进展。©2023作者。
The interaction between the tumor-microenvironment (TME) and the cancer cells has emerged as a key player in colorectal cancer (CRC) metastasis. A small proportion of CRC cells which undergo epithelial-mesenchymal transition (EMT) facilitate the reshaping of the TME by regulating various cellular ingredients.Immunohistochemical analysis, RNA immunoprecipitation (RIP), RNA Antisense Purification (RAP), dual luciferase assays were conducted to investigate the biological function and regulation of LINC00543 in CRC. A series in vitro and in vivo experiments were used to clarify the role of LINC00543 in CRC metastasis.Here we found that the long non-coding RNA LINC00543, was overexpressed in colorectal cancer tissues, which correlated with advanced TNM stage and poorer prognosis of CRC patients. The overexpression of LINC00543 promoted tumorigenesis and metastasis of CRC cells by enhancing EMT and remodeling the TME. Mechanistically, LINC00543 blocked the transport of pre-miR-506-3p across the nuclear-cytoplasmic transporter XPO5, thereby reducing the production of mature miR-506-3p, resulting in the increase in the expression of FOXQ1 and induction of EMT. In addition, upregulation of FOXQ1 induced the expression of CCL2 that accelerated the recruitment of macrophages and their M2 polarization.Our study showed that LINC00543 enhanced EMT of CRC cells through the pre-miR-506-3p/FOXQ1 axis. This resulted in the upregulation of CCL2, leading to macrophages recruitment and M2 polarization, and ultimately stimulating the progression of CRC.© 2023. The Author(s).