Department of General Surgery, The Second Hospital of Dalian Medical University, 116023, Dalian, China.
Department of Clinical Biochemistry, College of Laboratory Medicine, Dalian Medical University, 116044, Dalian, China.
Cell Death Dis. 2022 Jul 11;13(7):593. doi: 10.1038/s41419-022-05026-x.
Liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin) plays an important regulatory role in a variety of diseases, including tumors. However, the underlying mechanism of LSECtin in gastric cancer (GC) remains largely unknown. In our research, LSECtin promoted the adhesion and invasion of GC cells, and was involved in lymphatic metastasis of GC cells. Mechanistically, LSECtin promoted the adhesion, proliferation and migration of GC cells by downregulating STAT1 expression. The circular RNA circFBXL4, which is regulated by LSECtin, sponges the microRNA miR-146a-5p to regulate STAT1 expression. The promotion of GC cell proliferation, migration and invasion mediated by LSECtin was largely inhibited by circFBXL4 overexpression or miR-146a-5p silencing. Moreover, in its role as a transcription factor, STAT1 modulated the expression of FN1 and CHD4. In conclusion, LSECtin might be involved in the lymphatic metastasis of GC by upregulating the expression of FN1 and CHD4 via the circFBXL4/miR-146a-5p/STAT1 axis, possibly indicating a newly discovered pathogenic mechanism.
肝脏和淋巴结窦状内皮细胞 C 型凝集素 (LSECtin) 在多种疾病中发挥着重要的调节作用，包括肿瘤。然而，LSECtin 在胃癌 (GC) 中的潜在机制在很大程度上尚不清楚。在我们的研究中，LSECtin 促进了 GC 细胞的黏附和侵袭，并参与了 GC 细胞的淋巴转移。从机制上讲，LSECtin 通过下调 STAT1 表达促进 GC 细胞的黏附、增殖和迁移。由 LSECtin 调控的环状 RNA circFBXL4 通过海绵吸附 microRNA miR-146a-5p 来调节 STAT1 表达。LSECtin 介导的 GC 细胞增殖、迁移和侵袭的促进作用在很大程度上被 circFBXL4 过表达或 miR-146a-5p 沉默所抑制。此外，作为转录因子，STAT1 通过 circFBXL4/miR-146a-5p/STAT1 轴调节 FN1 和 CHD4 的表达。总之，LSECtin 可能通过上调 FN1 和 CHD4 的表达参与 GC 的淋巴转移，这可能表明了一个新发现的致病机制。
