Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts

Abstract

PurposeThe present review aimed to assess the role of exosomal miRNAs in cancer-associated fibroblasts (CAFs), normal fibroblasts (NFs), and cancer cells. The roles of exosomal miRNAs and miRNA dysregulation in CAF formation and activation were summarized.MethodsAll relevant publications were retrieved from the PubMed database, with key words such as CAFs, CAF, stromal fibroblasts, cancer-associated fibroblasts, miRNA, exosomal, exosome, and similar terms.ResultsRecent studies have revealed that CAFs, NFs, and cancer cells can secrete exosomal miRNAs to affect each other. Dysregulation of miRNAs and exosomal miRNAs influence the formation and activation of CAFs. Furthermore, miRNA dysregulation in CAFs is considered to be associated with a secretory phenotype change, tumor invasion, tumor migration and metastasis, drug resistance, and poor prognosis.ConclusionsFinding of exosomal miRNA secretion provides novel insights into communication among CAFs, NFs, and cancer cells. MicroRNA dysregulation is also involved in the whole processes of CAF formation and function. Dysregulation of miRNAs in CAFs can affect the secretory phenotype of the latter cells.

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

“…However, as we learn more about miRNAs, it is clear that generalization about a particular miRNA being oncogenic or a tumor suppressor depends on cellular context. miRNAs are involved in the post-transcriptional regulation of genes involved in EMT, stemness, cell signaling pathways, and regulation of the tumor microenvironment, including the conversion of normal fibroblasts into cancer-associated fibroblasts (CAFs) by transfer of exosomal miRNAs from tumor cells (reviewed in (Yang, et al 2017a)). An issue in the field is the lack of congruence of miRNAs identified for a particular cancer type, e.g., thyroid cancer, even within a subtype, in different studies.…”

“…CAFs stimulate cancer progression by secreting chemokines, cytokines, and growth factors that create the extracellular matrix (ECM) and CAFs secrete EVs containing a different spectrum of miRNAs compared to normal fibroblasts (Bayraktar et al 2017). Among the miRNAs secreted by CAFs that regulate cancer cells are miR-21, miR-143, and miR-378 in BCa (Donnarumma, et al 2017); miR-210, miR-409-3p/5p (Yang et al 2017a), andmiR-409 (Josson, et al 2014) in PCa cells; and miR-21 in ovarian cancer (Au Yeung, et al 2016). Tumor-associated macrophages (TAMs) are also donors of miRNAs in cancer (reviewed in (Bayraktar et al 2017)).…”

MiR-598 Suppresses Invasion and Migration by Negative Regulation of Derlin-1 and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer

“…A wide range of biological processes including cell proliferation, apoptosis, invasion, and migration have been identified to be regulated by miRNAs [7, 8]. Thus, the deregulated expression of miRNAs has been associated with various diseases including cancers [9-12].…”

Deregulated MicroRNAs in Cancer-Associated Fibroblasts from Front Tumor Tissues of Lung Adenocarcinoma as Potential Predictors of Tumor Promotion

“…Alternatively, the potential role of miRNAs secreted by exosomes in CAFs in the ability of cancer cells to migrate and invade cannot be ruled out. Exosomal miR-NAs can be taken up by bystander cells and functionally delivered as a mechanism of cell-to-cell communication (Bach et al 2017;Bayraktar et al 2017;Yang et al 2017). However, it has been demonstrated that the secreted miRNA expression pattern does not always match that of endogenous miRNAs (Valadi et al 2007;Pigati et al 2010).…”