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

来自 RBPJ 过表达巨噬细胞的外泌体 LncRNA LBX1-AS1 通过 miR-182-5p/FOXO3 抑制口腔鳞状细胞癌进展

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作者:Yilong Ai, Haigang Wei, Siyuan Wu, Zhe Tang, Xia Li, Chen Zou

Conclusion

Exo-LBX1-AS1 secreted from RBPJ-OE Mφ 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.

Methods

The long non-coding RNA (lncRNA) profiles in RBPJ-OE 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 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 Mφ-Exo-lncRNAs in vivo.

Results

It was uncovered that lncRNA LBX1-AS1 was upregulated in RBPJ-OE Mφ-Exos relative to that in WT Mφ-Exos. RBPJ-OE Mφ-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 Mφ-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.

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