Novel roles of LSECtin in gastric cancer cell adhesion, migration, invasion, and lymphatic metastasis

Abstract

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.

GC‑MSC‑derived circ_0024107 promotes gastric cancer cell lymphatic metastasis via fatty acid oxidation metabolic reprogramming mediated by the miR‑5572/6855‑5p/CPT1A axis

“…Over the past decades, an increasing number of tissue-and plasma-derived circRNAs have been demonstrated to be associated with the lymphatic metastasis of gastric cancer (23,24). CircRNAs are sometimes used to clarify the regulatory mechanisms of specific molecules involved in the lymph node metastasis of gastric cancer (25). A recent study determined circRNA profiles in cancer-associated fibroblasts (CAFs) and identified that CAF-specific circCUL2 conferred the CAF phenotype on normal fibroblasts and mediated the CAF oncogenic effects by modulating the miR-203a-3p/MyD88/NF-κB/IL6 axis (26).…”

Immune checkpoint inhibitors: breakthroughs in cancer treatment

“…According to a pre-clinical study, the binding of LSECtin to LAG-3 in a B16 melanoma model downregulates IFN-γ secretion, thereby blocking T cell immunity. Furthermore, LSECtin plays a role in the invasion and growth of gastric cancer cells, and eventually results in the development of gastric cancer 78 . FGL-1 directly downregulates the secretion of IL-2, thus conveying a negative regulatory signal 79 , whereas Gal-3 binds oncoproteins and elicits tumor cell proliferative effects.…”

Interplay between JAK/STAT pathway and non-coding RNAs in different cancers

“…Consequently, blockade of circFBXL4-mediated sponging effects on miR-146a-5p-led to reduction in the levels of STAT1 and subsequent upregulation of FN1 and CHD4 ( Fig. 5 ) [ 91 ]. Collectively, these findings indicated that migration and invasion of gastric cancer cells mediated by LSECtin was impaired significantly by overexpression of circFBXL4 or miR-146a-5p depletion.…”