M2 Macrophage-Derived Exosomal lncRNA AFAP1-AS1 and MicroRNA-26a Affect Cell Migration and Metastasis in Esophageal Cancer

Xifeng Mi; Rongyu Xu; Shunzhong Hong; Tingting Xu; Wanfei Zhang; Ming Liu

Molecular Therapy: Nucleic Acids (Dec 2020)

M2 Macrophage-Derived Exosomal lncRNA AFAP1-AS1 and MicroRNA-26a Affect Cell Migration and Metastasis in Esophageal Cancer

Xifeng Mi,
Rongyu Xu,
Shunzhong Hong,
Tingting Xu,
Wanfei Zhang,
Ming Liu

Affiliations

Xifeng Mi: Department of Gastroenterology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000 Fujian, China; Corresponding author: Xifeng Mi, PhD, Department of Gastroenterology, Quanzhou First Hospital Affiliated to Fujian Medical University, No. 250, Dongjie Street, Licheng District, Quanzhou, 362000 Fujian, China.
Rongyu Xu: Department of Oncology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000 Fujian, China
Shunzhong Hong: Department of Gastroenterology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000 Fujian, China
Tingting Xu: Department of Gastroenterology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000 Fujian, China
Wanfei Zhang: Department of Oncology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000 Fujian, China
Ming Liu: Digestive Endoscopy Center of the First Affiliated Hospital of Xiamen University, Xiamen, 361000 Fujian, China

Journal volume & issue: Vol. 22
pp. 779 – 790

Abstract

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Exosomes from cancer cells or immune cells, carrying bio-macromolecules or long non-coding RNAs (lncRNAs), participate in tumor pathogenesis and progression by modulating the microenvironment. This study aims to explore the function of M2 macrophage-derived exosomes on the invasion and metastasis of esophageal cancer (EC) with the involvement of the lncRNA AFAP1-AS1/microRNA-26a (miR-26a)/activating transcription factor 2 (ATF2) axis. We found that lncRNA AFAP1-AS1 could specifically bind to miR-26a, thus affecting the expression of miR-26a, and ATF2 was the direct target of miR-26a. Compared with M1 macrophage-derived exosomes, M2 macrophage-derived exosomes exhibited higher AFAP1-AS1 and ATF2 expression and lower miR-26a expression. Moreover, extracellular AFAP1-AS1 could be moved to KYSE410 cells via being incorporated into M2 macrophage-derived exosomes. M2 macrophage-derived exosomes could downregulate miR-26a and promote the expression of ATF2 through high expression of AFAP1-AS1, thus promoting the migration, invasion, and lung metastasis of EC cells; M2-exosomes upregulating AFAP1-AS1 or downregulating miR-26a ameliorated this effect. In summary, M2 macrophage-derived exosomes transferred lncRNA AFAP1-AS1 to downregulate miR-26a and upregulate ATF2, thus promoting the invasion and metastasis of EC. Targeting M2 macrophages and the lncRNA AFAP1-AS1/miR-26a/ATF2 signaling axis represents a potential therapeutic strategy for EC.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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