Osteosarcoma Cell-Derived Exosomal ELFN1-AS1 Mediates Macrophage M2 Polarization Sponging MiR-138-5p and MiR-1291 to Promote the Tumorgenesis of Osteosarcoma

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jul 5

PMID 35785218

Authors

Bangmin Wang

Xin Wang

Po Li

Xiaoying Niu

Xiaoxiao Liang

Guancong Liu

Zhiyong Liu

Hong Ge

Affiliations

Soon will be listed here.

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 xenograft mouse model was established to assess the role of ELFN1-AS1 . 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 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 sponging miR-138-5p and miR-1291 in macrophage .

Conclusion: OS cell-derived exosomal ELFN1-AS1 was able to induce macrophage M2 polarization 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.

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