Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression

Abstract

Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25–3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25–3p and miR-92a-3p stimulated secretion of pro-inflammatory cytokine IL-6 from tumor-associated macrophages (TAM) in a TLR7/8-dependent manner, which in turn promoted LPS cell proliferation, invasion, and metastasis via this interaction with the surrounding microenvironment. Our findings provide novel and previously unreported insight into LPS progression, identifying communication between LPS cells and their microenvironment as a process critically involved in LPS progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy. Precis: Two extracellular vesicle-derived microRNAs are found to drive liposarcoma progression by stimulating the secretion of pro-inflammatory IL-6 from tumor-associated macrophages, offering new theranostic opportunities in this cancer setting.

Microenvironment‐induced TIMP2 loss by cancer‐secreted exosomal miR‐4443 promotes liver metastasis of breast cancer

“…In recent years, exosomes have been subject of increasing interest in the diagnosis and prognosis of tumors (Alegre et al, 2016; Melo et al, 2015). These small vesicles also exert their biological function to deliver kinds of targeted drugs, such as miRNAs and small interfering RNAs (Casadei et al, 2017; H. Zhang et al, 2017; Y. Zhang et al, 2014). Lately, the exploration of miRNAs and their exosomes suggest a potential role of these regulatory factors in discovering the metastatic potential of cancer cells and mediating cancer‐host communication.…”

Injured liver-released miRNA-122 elicits acute pulmonary inflammation via activating alveolar macrophage TLR7 signaling pathway

“…Recent studies showed that mature miRNAs with GU-rich sequences also contribute to immune stimulation by serving as physiological ligands for murine TLR7 and human TLR8 (15). For example, miR-21, miR-29a, miR-25-3p, and miR-92a-3p, all harboring GU-rich sequences, have been shown to interact with murine TLR7 and human TLR8 to activate the secretion of proinflammatory cytokines in macrophages (15)(16)(17). Consistent with this, Lehmann et al (18) found that another GU-enriched miRNA, let-7b, acts as a potent activator of TLR7 signaling in neurons, which induces neurodegeneration.…”

WITHDRAWN: Expression profiles and biological implications of plasma miRNAs associated with chronic myeloid leukemia phases

“…Oncotarget s470 www.impactjournals.com/oncotarget immune-modulation, angiogenesis, pathogenesis and progression of cancers [7][8][9][10]. Dysregulated circulatory miRNAs have been served as biomarkers for diagnosis, prognosis and prediction in hematopoietic neoplasias [11].…”