Department of Radiation Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Department of Radiation Oncology, Shanghai East Hospital Ji'an hospital, Ji'an City, Jiangxi Province, 343000, China.
Cell Death Dis. 2024 Aug 27;15(8):630. doi: 10.1038/s41419-024-07004-x.
Lymph node metastasis (LNM) is a common invasive feature of hepatocellular carcinoma (HCC) associated with poor clinical outcomes. Through microarray profiling and bioinformatic analyses, we identified the circ-0044539-miR-29a-3p-VEGFA axis as a potential key factor in the progression of HCC LNM. In HCC cells and nude mice, circ-0044539 downregulation or miR-29a-3p upregulation was associated with small tumor size, PI3K-AKT-mTOR pathway inactivation, and downregulation of the key LNM factors (HIF-1α and CXCR4). Furthermore, circ-0044539 was also responsible for exosomal miR-29a-3p secretion. Exosomal miR-29a-3p was then observed to migrate to the LNs and downregulate High-mobility group box transcription factor 1 (Hbp1) in Polymorphonuclear Myeloid-derived suppressor cells (PMN-MDSCs), inducing the formation of a microenvironment suitable for tumor colonization. Overall, circ-0044539 promotes HCC cell LNM abilities and induces an immune-suppressive environment in LNs through exosomes, highlighting its potential as a target for HCC LNM and HCC immunotherapy.
淋巴结转移（LNM）是与不良临床结局相关的肝细胞癌（HCC）的常见侵袭特征。通过微阵列分析和生物信息学分析，我们确定 circ-0044539-miR-29a-3p-VEGFA 轴是 HCC LNM 进展的潜在关键因素。在 HCC 细胞和裸鼠中，circ-0044539 的下调或 miR-29a-3p 的上调与肿瘤体积小、PI3K-AKT-mTOR 通路失活以及关键 LNM 因子（HIF-1α和 CXCR4）的下调有关。此外，circ-0044539 还负责外泌体 miR-29a-3p 的分泌。然后观察到外泌体 miR-29a-3p 迁移到 LNs 并下调多形核髓样来源抑制细胞（PMN-MDSCs）中的高迁移率族盒转录因子 1（Hbp1），诱导适合肿瘤定植的微环境的形成。总体而言，circ-0044539 通过外泌体促进 HCC 细胞 LNM 能力，并在 LNs 中诱导免疫抑制环境，突出了其作为 HCC LNM 和 HCC 免疫治疗靶点的潜力。
