Nedaeinia Reza, Najafgholian Simin, Salehi Rasoul, Goli Mohammad, Ranjbar Maryam, Nickho Hamid, Haghjooy Javanmard Shaghayegh, A Ferns Gordon, Manian Mostafa
Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Emergency Medicine, School of Medicine, Valiasr Hospital, Arak University of Medical Sciences, Arak, Iran.
Cell Death Discov. 2024 Aug 26;10(1):380. doi: 10.1038/s41420-024-02146-5.
CAFs (cancer-associated fibroblasts) are highly flexible cells of the cancer microenvironment. They produce the extracellular matrix (ECM) constituents that form the structure of the tumor stroma but are also a source of metabolites, growth factors, chemokines, and exosomes that impact every aspect of the tumor, including its response to treatment. It is believed that exosomal miRNAs facilitate intercellular signaling, which is essential for the development of cancer. The role of miRNAs and CAFs in the tumor microenvironment (TME) and carcinogenesis is reviewed in this paper. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines were used to perform a systematic review. Several databases, including Web of Science, Medline, Embase, Cochrane Library, and Scopus, were searched using the following keywords: CAFs, CAF, cancer-associated fibroblasts, stromal fibroblasts, miRNA, exosomal miRNAs, exosome and similar terms. We identified studies investigating exosomal miRNAs and CAFs in the TME and their role in carcinogenesis. A total of 12,572 papers were identified. After removing duplicates (n = 3803), 8774 articles were screened by title and abstract. Of these, 421 were excluded from further analysis. It has been reported that if exosomal miRNAs in CAFs are not functioning correctly, this may influence the secretory phenotype of tip cells and contribute to increased tumor invasiveness, tumor spread, decreased treatment efficacy, and a poorer prognosis. Under their influence, normal fibroblasts (NFs) are transformed into CAFs. Furthermore, they participate in metabolic reprogramming, which allows for fast proliferation of the cancer cell population, adaptation to growing energy demands, and the capacity to avoid immune system identification.
癌症相关成纤维细胞（CAFs）是癌症微环境中高度灵活的细胞。它们产生构成肿瘤基质结构的细胞外基质（ECM）成分，但也是代谢物、生长因子、趋化因子和外泌体的来源，这些物质会影响肿瘤的各个方面，包括其对治疗的反应。据信，外泌体微小RNA（miRNAs）促进细胞间信号传导，这对癌症的发展至关重要。本文综述了miRNAs和CAFs在肿瘤微环境（TME）及致癌作用中的作用。使用系统评价和Meta分析的首选报告项目（PRISMA）2020指南进行系统评价。使用以下关键词在包括Web of Science、Medline、Embase、Cochrane图书馆和Scopus在内的多个数据库中进行检索：CAFs、CAF、癌症相关成纤维细胞、基质成纤维细胞、miRNA、外泌体miRNAs、外泌体及类似术语。我们确定了研究TME中外泌体miRNAs和CAFs及其在致癌作用中作用的研究。共识别出12572篇论文。去除重复项（n = 3803）后，通过标题和摘要筛选出8774篇文章。其中，421篇被排除在进一步分析之外。据报道，如果CAFs中的外泌体miRNAs功能不正常，这可能会影响顶端细胞的分泌表型，并导致肿瘤侵袭性增加、肿瘤扩散、治疗效果降低和预后较差。在它们的影响下，正常成纤维细胞（NFs）会转化为CAFs。此外，它们参与代谢重编程，这使得癌细胞群体能够快速增殖，适应不断增长的能量需求，并具备避免被免疫系统识别的能力。
