M2 macrophage-derived exosomal miR-1911-5p promotes cell migration and invasion in lung adenocarcinoma by down-regulating CELF2-activated ZBTB4 expression

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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.

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Lung Cancer 2020

Brett C Bade, Charles S. Dela Cruz (2020)

Despite advances in our understanding of risk, development, immunologic control, and treatment options for lung cancer, it remains the leading cause of cancer death. Tobacco smoking remains the predominant risk factor for lung cancer development. Nontobacco risk factors include environmental and occupational exposures, chronic lung disease, lung infections, and lifestyle factors. Because tobacco remains the leading risk factor for lung cancer, disease prevention is focused on smoking avoidance and cessation. Other prevention measures include healthy diet choices and maintaining a physically active lifestyle. Future work should focus on smoking cessation campaigns and better understanding disease development and treatment strategies in nonsmokers.

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Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications

Yuxin Lin, Jianxin Xu, Huiyin Lan (2019)

Tumor metastasis is a major contributor to the death of cancer patients. It is driven not only by the intrinsic alterations in tumor cells, but also by the implicated cross-talk between cancer cells and their altered microenvironment components. Tumor-associated macrophages (TAMs) are the key cells that create an immunosuppressive tumor microenvironment (TME) by producing cytokines, chemokines, growth factors, and triggering the inhibitory immune checkpoint proteins release in T cells. In doing so, TAMs exhibit important functions in facilitating a metastatic cascade of cancer cells and, meanwhile, provide multiple targets of certain checkpoint blockade immunotherapies for opposing tumor progression. In this article, we summarize the regulating networks of TAM polarization and the mechanisms underlying TAM-facilitated metastasis. Based on the overview of current experimental evidence dissecting the critical roles of TAMs in tumor metastasis, we discuss and prospect the potential applications of TAM-focused therapeutic strategies in clinical cancer treatment at present and in the future.

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Global Epidemiology of Lung Cancer

Julie Barta, Charles Powell, Juan Wisnivesky (2019)

While lung cancer has been the leading cause of cancer-related deaths for many years in the United States, incidence and mortality statistics – among other measures – vary widely worldwide. The aim of this study was to review the evidence on lung cancer epidemiology, including data of international scope with comparisons of economically, socially, and biologically different patient groups. In industrialized nations, evolving social and cultural smoking patterns have led to rising or plateauing rates of lung cancer in women, lagging the long-declining smoking and cancer incidence rates in men. In contrast, emerging economies vary widely in smoking practices and cancer incidence but commonly also harbor risks from environmental exposures, particularly widespread air pollution. Recent research has also revealed clinical, radiologic, and pathologic correlates, leading to greater knowledge in molecular profiling and targeted therapeutics, as well as an emphasis on the rising incidence of adenocarcinoma histology. Furthermore, emergent evidence about the benefits of lung cancer screening has led to efforts to identify high-risk smokers and development of prediction tools. This review also includes a discussion on the epidemiologic characteristics of special groups including women and nonsmokers. Varying trends in smoking largely dictate international patterns in lung cancer incidence and mortality. With declining smoking rates in developed countries and knowledge gains made through molecular profiling of tumors, the emergence of new risk factors and disease features will lead to changes in the landscape of lung cancer epidemiology.

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Author and article information

Journal

Title: Anti-Cancer Drugs

Publisher: Ovid Technologies (Wolters Kluwer Health)

ISSN (Print): 0959-4973

Publication date Created: 2023

Publication date (Electronic): November 18 2022

Publication date (Print): February 2023

Volume: 34

Issue: 2

Pages: 238-247

Affiliations

[1 ]Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan

[2 ]Department of Thoracic Surgery, the First Affiliated Hospital of Yangtze University, Jingzhou

[3 ]Department of Oncology, the First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China

Article

DOI: 10.1097/CAD.0000000000001414

PubMed ID: 36730375

SO-VID: 9acb6c44-5074-4a3a-b71a-60ecd9856c88

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