Exosomal LncRNA LBX1-AS1 Derived From RBPJ Overexpressed-Macrophages Inhibits Oral Squamous Cell Carcinoma Progress via miR-182-5p/FOXO3

Objectives Macrophage-derived exosomes (M phi-Exos) are involved in tumor onset, progression, and metastasis, but their regulation in oral squamous cell carcinoma (OSCC) is not fully understood. RBPJ is implicated in macrophage activation and plasticity. In this study, we assessed the role of M phi-Exos with RBPJ overexpression (RBPJ-OE M phi-Exos) in OSCC. Materials and Methods The long non-coding RNA (lncRNA) profiles in RBPJ-OE M phi-Exos and THP-1-like macrophages (WT M phi)-Exos were evaluated using lncRNA microarray. Then the functions of M phi-Exo-lncRNA in OSCC cells were assessed via CCK-8, EdU, and Transwell invasion assays. Besides, luciferase reporter assay, RNA immunoprecipitation, and Pearson's correlation analysis were adopted to confirm interactions. Ultimately, a nude mouse model of xenografts was used to further analyze the function of M phi-Exo-lncRNAs in vivo. Results It was uncovered that lncRNA LBX1-AS1 was upregulated in RBPJ-OE M phi-Exos relative to that in WT M phi-Exos. RBPJ-OE M phi-Exos and LBX1-AS1 overexpression inhibited OSCC cells to proliferate and invade. Meanwhile, LBX1-AS1 knockdown boosted the tumor to grow in vivo. The effects of RBPJ-OE M phi-Exos on OSCC cells can be reversed by the LBX1-AS1 knockdown. Additionally, mechanistic investigations revealed that LBX1-AS1 acted as a competing endogenous RNA of miR-182-5p to regulate the expression of FOXO3. Conclusion Exo-LBX1-AS1 secreted from RBPJ-OE M phi inhibits tumor progression through the LBX1-AS1/miR-182-5p/FOXO3 pathway, and LBX1-AS1 is probably a diagnostic biomarker and potential target for OSCC therapy.

Automated summary

Exo-LBX1-AS1 secreted from RBPJ-OE M phi inhibits tumor progression through the LBX1-AS1/miR-182-5p/FOXO3 pathway, and LBX1-AS1 may serve as a diagnostic biomarker and potential therapeutic target for OSCC.