Department of General Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, No.188, Shizi Street, Suzhou, 215006, Jiangsu Province, People's Republic of China.
Department of General Surgery, Yancheng City No. 1 People's Hospital, Yancheng, 224300, Jiangsu Province, People's Republic of China.
Mol Cell Biochem. 2024 Jan;479(1):13-27. doi: 10.1007/s11010-023-04709-z. Epub 2023 Mar 29.
Cancer cells-derived exosomal lncRNAs could modulate the tumorigenesis of colorectal cancer (CRC) via modulating macrophage M2 polarization. However, the clarified mechanism and function of lncRNA BANCR in CRC remains unclear. Exosomes were identified by TEM, NTA, western blot and fluorescent staining. M2 macrophages were identified by CD206 and CD163 expressions using by flow cytometry and RT-qPCR. In addition, the relation between IGF2BP2 and BANCR or RhoA were explored by RIP assay. The malignant behaviors of CRC cells were examined by CCK-8, EdU and transwell assays. Histopathological changes in mice were observed by H&E staining. Silencing of BANCR notably inhibited the proliferation, migration and invasion of CRC cells. SW620 and HCT-15 cells-derived exosomal BANCR positively regulated the macrophage M2 polarization. In addition, exosomal BANCR remarkably enhanced the promoting roles mediated by M2 macrophages on proliferation and invasion in CRC cells. Meanwhile, exosomal BANCR promoted the M2 macrophage polarization via activation of RhoA/Rock pathway by recruiting IGF2BP2. Inhibition of RhoA/Rock pathway reversed exosomal BANCR-mediated macrophages M2 polarization and CRC malignant behaviors in SW620 and HCT-15 cells. Exosomal lncRNA BANCR derived from SW620 and HCT-15 cells promoted the metastasis of CRC via inducing the polarization of M2 macrophages. Thus, BANCR might be a new target for the treatment of CRC.
癌细胞来源的外泌体 lncRNA 可以通过调节巨噬细胞 M2 极化来调节结直肠癌（CRC）的发生。然而，lncRNA BANCR 在 CRC 中的明确机制和功能仍不清楚。通过 TEM、NTA、western blot 和荧光染色鉴定外泌体。通过流式细胞术和 RT-qPCR 检测 CD206 和 CD163 的表达来鉴定 M2 巨噬细胞。此外，通过 RIP 测定探索 IGF2BP2 与 BANCR 或 RhoA 之间的关系。通过 CCK-8、EdU 和 Transwell 测定检查 CRC 细胞的恶性行为。通过 H&E 染色观察小鼠的组织病理学变化。沉默 BANCR 明显抑制 CRC 细胞的增殖、迁移和侵袭。SW620 和 HCT-15 细胞衍生的外泌体 BANCR 正向调节巨噬细胞 M2 极化。此外，外泌体 BANCR 通过募集 IGF2BP2 激活 RhoA/Rock 通路，显著增强 M2 巨噬细胞对 CRC 细胞增殖和侵袭的促进作用。同时，抑制 RhoA/Rock 通路逆转了外泌体 BANCR 介导的巨噬细胞 M2 极化和 SW620 和 HCT-15 细胞中 CRC 的恶性行为。来自 SW620 和 HCT-15 细胞的外泌体 lncRNA BANCR 通过诱导 M2 巨噬细胞极化促进 CRC 的转移。因此，BANCR 可能是 CRC 治疗的新靶点。
