The EGFR Signaling Modulates in Mesenchymal Stem Cells the Expression of miRNAs Involved in the Interaction with Breast Cancer Cells

Abstract

We previously demonstrated that the epidermal growth factor receptor (EGFR) modulates in mesenchymal stem cells (MSCs) the expression of a number of genes coding for secreted proteins that promote breast cancer progression. However, the role of the EGFR in modulating in MSCs the expression of miRNAs potentially involved in the progression of breast cancer remains largely unexplored. Following small RNA-sequencing, we identified 36 miRNAs differentially expressed between MSCs untreated or treated with the EGFR ligand transforming growth factor α (TGFα), with a fold change (FC) < 0.56 or FC ≥ 1.90 (CI, 95%). KEGG analysis revealed a significant enrichment in signaling pathways involved in cancer development and progression. EGFR activation in MSCs downregulated the expression of different miRNAs, including miR-23c. EGFR signaling also reduced the secretion of miR-23c in conditioned medium from MSCs. Functional assays demonstrated that miR-23c acts as tumor suppressor in basal/claudin-low MDA-MB-231 and MDA-MB-468 cells, through the repression of IL-6R. MiR-23c downregulation promoted cell proliferation, migration and invasion of these breast cancer cell lines. Collectively, our data suggested that the EGFR signaling regulates in MSCs the expression of miRNAs that might be involved in breast cancer progression, providing novel information on the mechanisms that regulate the MSC-tumor cell cross-talk.

Investigating microRNA Profiles in Prostate Cancer Bone Metastases and Functional Effects of microRNA-23c and microRNA-4328

“…The interpretation of those caveats is not clear. Nevertheless, the suggested miRNAs-23c and -4328 have been scientifically studied and suggested to be of functional relevance in cancer [23,[53][54][55][56][57][58][59]. The tissue localization of the miRNA-23c and -4328 will need to be confirmed.…”

A CCL2+DPP4+ subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans

“…To investigate how cMo-1s regulate adipogenesis and identify tractable therapeutic targets, the ligand-receptor analysis was performed, which demonstrated that cMo-1s might promote proinflammatory and pro-adipogenic mediator expression in MSC1-S1s (Supplementary Data 20). Correspondingly, cMo-1s expressed higher levels of epidermal growth factor receptor ligands known to regulate MSC activation 26 . Interestingly, the results suggested that both cMo-1s and MSC1-S1s in CF were major producers of adipokines and cytokines such as IL-6, but the IL-6 receptor differed in these subsets (IL-6R and HRH1, respectively) (Fig.…”

Heterogeneidade relacionada ao câncer de mama representada em miRNAs circulantes e vesiculares: resultados de ensaios de alto rendimento e prova de conceito para seleção de vesículas extracelulares derivadas de tumor

“…In particular, the hsa-miR-122-5p has been identified in liquid biopsies of BC patients, especially in more aggressive subtypes and models [76,144,196,197]. Interestingly, Gallo et al (2022) demonstrated that mesenchymal stem cells (MSCs) export hsa-miR-23c which seems to control the growth of TNBC cells [198]. Although the hypothesis that MSCs express hsa-miR-23c and this miRNA can reach the bloodstream is valid, it is somewhat difficult to define whether the miRNA present in plasma comes from MSCs or tumor cells, complicating diagnostic approaches of this putative biomarker.…”

“…(2022) described a mechanism to induce a cross-talk between Mesenchymal Stem Cells (MSCs) and TNBC cells [198]. Then, it was proven that hsa-miR-513a-5p can inhibit the expression of progesterone receptors in BC tissues [374].…”