Original articleM2 macrophage-derived exosomal miR-1911-5p promotes cell migration and invasion in lung adenocarcinoma by down-regulating CELF2-activated ZBTB4 expressionGuan, Bingfenga; Dai, Xiaofengb; Zhu, Yanc; Geng, Qinga Author Information aDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan bDepartment of Thoracic Surgery, the First Affiliated Hospital of Yangtze University, Jingzhou cDepartment of Oncology, the First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China Received 14 April 2022 Revised form accepted 14 April 2022 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.anti-cancerdrugs.com. Correspondence to Qing Geng, PhD, Department of Thoracic Surgery, Renmin Hospital of Wuhan University, No. 238, Jiefang Rd, Wuhan, 430060 Hubei, China, Tel: +86 27 88041911; e-mail: [email protected] Anti-Cancer Drugs: November 18, 2022 - Volume - Issue - 10.1097/CAD.0000000000001414 doi: 10.1097/CAD.0000000000001414 Buy SDC PAP Metrics Abstract Lung adenocarcinoma (LUAD) is one of the most aggressive, lethal cancers, comprising around 40% of lung cancer cases. Metastases are the primary cause of LUAD deaths. The mechanism underlying metastatic LUAD and tumor microenvironment remain largely unknown. To explore the effect of M2 macrophage-derived exosomes on LUAD progression. Quantitative-PCR (q-PCR) and western blot were used to measure the expression of RNAs and proteins separately. Co-culture experiments wound healing and Transwell invasion assays were performed to evaluate the effect of M2 macrophage-derived exosomes on LUAD cell migration and invasion. RNA pulldown and luciferase reporter, RNA-binding immunoprecipitation (RIP), and mRNA stability assays were conducted to explore the downstream mechanism of exosomal microRNA-1911-5p (miR-1911-5p). M2 macrophage-derived exosomes accelerated the migration and invasion of LUAD cells. M2 macrophages-secreted exosomal miR-1911-5p enhanced cell migration and invasion in LUAD. Mechanically, miR-1911-5p targeted CUGBP- and ETR-3-like family 2 (CELF2) to downregulate zinc finger and BTB domain containing 4 (ZBTB4) in LUAD. Additionally, miR-1911-5p promoted LUAD progression via ZBTB4. The present study demonstrated that M2 macrophage-derived exosomal miR-1911-5p facilitates the migration and invasion of LUAD cells by inhibiting CELF2-activated ZBTB4, which might offer insight into LUAD treatment. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.