Circ-0044539 通过外泌体-miR-29a-3p 促进肝细胞癌的淋巴结转移。
Circ-0044539 promotes lymph node metastasis of hepatocellular carcinoma through exosomal-miR-29a-3p.
发表日期：2024 Aug 27
作者：
Yi Yang, Xue-Qin Chen, Ya-Xun Jia, Jie Ma, Di Xu, Zuo-Lin Xiang
来源：
Cell Death & Disease
摘要：
淋巴结转移（LNM）是肝细胞癌（HCC）的常见侵袭性特征，与不良临床结果相关。通过微阵列分析和生物信息学分析，我们确定了 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 下调或 miR-29a-3p 上调与肿瘤尺寸小、PI3K-AKT-mTOR 通路失活以及关键 LNM 因子（HIF-1α 和 CXCR4）下调相关。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 LN 并下调多形核骨髓源性抑制细胞 (PMN-MDSC) 中的高迁移率组盒转录因子 1 (Hbp1)，诱导形成适合肿瘤定植的微环境。总体而言，circ-0044539 可促进 HCC 细胞 LNM 能力，并通过外泌体在 LN 中诱导免疫抑制环境，凸显其作为 HCC LNM 和 HCC 免疫治疗靶点的潜力。© 2024。作者。
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.© 2024. The Author(s).