AUTHOR=Wang Bangmin , Wang Xin , Li Po , Niu Xiaoying , Liang Xiaoxiao , Liu Guancong , Liu Zhiyong , Ge Hong TITLE=Osteosarcoma Cell-Derived Exosomal ELFN1-AS1 Mediates Macrophage M2 Polarization via Sponging miR-138-5p and miR-1291 to Promote the Tumorgenesis of Osteosarcoma JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.881022 DOI=10.3389/fonc.2022.881022 ISSN=2234-943X ABSTRACT=Background

Exosomes play an important role in cell-cell communication by transferring genetic materials such as long non-coding RNAs (lncRNAs) between cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Recent studies revealed that lncRNA ELFN1-AS1 could function as an oncogene in many human cancers. However, the role of extracellular lncRNA ELFN1-AS1 in cell-to-cell communication of osteosarcoma (OS) has not been fully investigated.

Methods

Functional studies, including CCK-8, EdU staining and transwell assay were performed to investigate the role of ELFN1-AS1 in the progression of OS. 143B via xenograft mouse model was established to assess the role of ELFN1-AS1 in vivo. In addition, transmission electron microscopy (TEM) and real-time quantitative PCR (RT-qPCR) assay were used to verify the existence of exosomal ELFN1-AS1.

Results

The level of ELFN1-AS1 was markedly upregulated in patients with advanced OS and in OS cells. In addition, overexpression of ELFN1-AS1 significantly promoted the proliferation, migration and invasion of OS cells, while knockdown of ELFN1-AS1 exhibited the opposite effects. Meanwhile, ELFN1-AS1 could be transferred from OS cells to macrophages via exosomes. Exosomal ELFN1-AS1 from 143B cells was able to promote macrophage M2 polarization, and M2 macrophage in return facilitated OS progression. Mechanistically, overexpression of ELFN1-AS1 upregulated CREB1 level via sponging miR-138-5p and miR-1291 in macrophage via.

Conclusion

OS cell-derived exosomal ELFN1-AS1 was able to induce macrophage M2 polarization via sponging miR-138-5p and miR-1291, and M2 macrophage notably facilitated the progression of OS. These data suggested that ELFN1-AS1 might serve as a potential therapeutic target for osteosarcoma.