AUTHOR=Ai Yilong , Wei Haigang , Wu Siyuan , Tang Zhe , Li Xia , Zou Chen 

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.605884

DOI=10.3389/fonc.2021.605884

ISSN=2234-943X

ABSTRACT=<sec><title>Objectives</title><p>Macrophage-derived exosomes (Mφ-Exos) are involved in tumor onset, progression, and metastasis, but their regulation in oral squamous cell carcinoma (OSCC) is not fully understood. <italic>RBPJ</italic> is implicated in macrophage activation and plasticity. In this study, we assessed the role of Mφ-Exos with <italic>RBPJ</italic> overexpression (<italic>RBPJ-OE</italic> Mφ-Exos) in OSCC.</p></sec><sec><title>Materials and Methods</title><p>The long non-coding RNA (lncRNA) profiles in <italic>RBPJ-OE</italic> Mφ-Exos and THP-1-like macrophages (WT Mφ)-Exos were evaluated using lncRNA microarray. Then the functions of Mφ-Exo-lncRNA in OSCC cells were assessed <italic>via</italic> 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 Mφ-Exo-lncRNAs <italic>in vivo</italic>.</p></sec><sec><title>Results</title><p>It was uncovered that lncRNA <italic>LBX1-AS1</italic> was upregulated in <italic>RBPJ-OE</italic> Mφ-Exos relative to that in WT Mφ-Exos. <italic>RBPJ-OE</italic> Mφ-Exos and <italic>LBX1-AS1</italic> overexpression inhibited OSCC cells to proliferate and invade. Meanwhile, <italic>LBX1-AS1</italic> knockdown boosted the tumor to grow <italic>in vivo</italic>. The effects of <italic>RBPJ-OE</italic> Mφ-Exos on OSCC cells can be reversed by the <italic>LBX1-AS1</italic> knockdown. Additionally, mechanistic investigations revealed that <italic>LBX1-AS1</italic> acted as a competing endogenous RNA of miR-182-5p to regulate the expression of <italic>FOXO3</italic>.</p></sec><sec><title>Conclusion</title><p>Exo-<italic>LBX1-AS1</italic> secreted from <italic>RBPJ-OE</italic> Mφ inhibits tumor progression through the <italic>LBX1-AS1</italic>/miR-182-5p/<italic>FOXO3</italic> pathway, and <italic>LBX1-AS1</italic> is probably a diagnostic biomarker and potential target for OSCC therapy.</p></sec>