Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, Hubei, China.
Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, Hubei, China.
J Transl Med. 2023 Feb 25;21(1):153. doi: 10.1186/s12967-023-04009-6.
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.
肿瘤微环境（TME）与癌细胞之间的相互作用已成为结直肠癌（CRC）转移的关键因素。一小部分经历上皮-间充质转化（EMT）的 CRC 细胞通过调节各种细胞成分来重塑 TME。
通过免疫组织化学分析、RNA 免疫沉淀（RIP）、RNA 反义纯化（RAP）、双荧光素酶测定来研究 LINC00543 在 CRC 中的生物学功能和调控作用。进行了一系列的体外和体内实验来阐明 LINC00543 在 CRC 转移中的作用。
我们发现长链非编码 RNA LINC00543 在结直肠癌组织中过表达，与 CRC 患者的晚期 TNM 分期和较差的预后相关。LINC00543 的过表达通过增强 EMT 和重塑 TME 促进 CRC 细胞的发生和转移。机制上，LINC00543 阻断了 pre-miR-506-3p 通过核质转运蛋白 XPO5 的运输，从而减少成熟 miR-506-3p 的产生，导致 FOXQ1 的表达增加并诱导 EMT。此外，FOXQ1 的上调诱导了 CCL2 的表达，加速了巨噬细胞的募集及其 M2 极化。
我们的研究表明，LINC00543 通过 pre-miR-506-3p/FOXQ1 轴增强 CRC 细胞的 EMT。这导致 CCL2 的上调，导致巨噬细胞募集和 M2 极化，并最终刺激 CRC 的进展。
