microRNA-378a-5p iS a novel positive regulator of melanoma progression

Abstract

Evaluating the expression levels of miR-378a-5p both in a large melanoma patient cohort from The Cancer Genome Atlas database and in melanoma patients from our Institute, we found that miR-378a-5p is upregulated in metastatic melanoma specimens. miR-378a-5p expression was also increased in melanoma cells resistant to target therapy, and decreased in response to drug treatment. We also demonstrated that overexpression of miR-378a-5p enhances in vitro cell invasion and migration, and facilitates the ability of melanoma cells to form de novo vasculogenic structures. While performing downstream targeting studies, we confirmed the ability of miR-378a-5p to modulate the expression of known target genes, such as SUFU, FUS-1, and KLF9. Luciferase-3′UTR experiments also identified STAMBP and HOXD10 as new miR-378a-5p target genes. MMP2 and uPAR, two HOXD10 target genes, were positively regulated by miR-378a-5p. Genetic and pharmacologic approaches inhibiting uPAR expression and activity evidenced that the in vitro tumor-promoting functions of miR-378a-5p, were in part mediated by uPAR. Of note miR-378a-5p was also able to increase VEGF, as well as in vitro and in vivo angiogenesis. Finally, genetic and pharmacologic modulation of Bcl-2 evidenced Bcl-2 ability to regulate miR-378a-5p expression. In conclusion, to the best of our knowledge, this is the first study demonstrating that miR-378a-5p acts as an oncogenic microRNA in melanoma.

The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma

“…EVs are broadly classified into four subtypes based upon vesicle size: 1) exosomes (30-150 nm), 2) microvesicles (50-1000 nm), 3) large vesicles (>1000 nm) and 4) apoptotic bodies (>1000 nm) (81). As to metastatic melanoma, most studies have assessed the role of miRNAs as predictors of response to targeted therapies in BRAF-mutant patients (82)(83)(84)(85). For example, we have demonstrated that a mini-signature composed of four miRNAs, i.e.…”

RNA-Associated Co-expression Network Identifies Novel Biomarkers for Digestive System Cancer

“…Previous studies indicate that gastric cancer stem-like cells are derived from MKN-45- by the expression change of hsa-let-7b-3p ( Salehi et al, 2018 ). Moreover, microRNA-378a-5p increased the expression level in melanoma cells and is a novel positive regulator of melanoma progression ( Tang et al, 2018 ; Tupone et al, 2020 ). The expression of hsa-miR-26a-5p was downregulated in breast cancer tissues and appeared to have a poor prognosis for patients ( Huang et al, 2019 ).…”

Inhibition of lysine acetyltransferases impairs tumor angiogenesis acting on both endothelial and tumor cells

“…After 72 h, cells were processed as previously reported [20]. For migration and invasion assays, 5 × 10 4 HUVEC were seeded into upper chamber of Transwell (Corning, Costar, New York, USA) or CultreCoat cell invasion chamber (Trevigen, Gaithersburg, MD, USA), respectively processing them after 6 h as previously reported [21]. For tube formation assay, 2.5 × 10 4 HUVEC or 5 × 10 4 lung cancer cells were seeded in duplicates in 24-well culture plates containing polymerized matrigel (BD Bioscience, San Jose, CA, USA) and incubated with CPTH6 for 6 or 18 h, respectively.…”

“…All procedures involving animals were authorized by the decree n. 26/2014 of the Italian Ministry of Health, authorization n. 787/2015PR-29/07/ 2015. In vivo angiogenesis matrigel assay was performed as previously reported [21]. Tumor vascularization of LCSC136 xenografts after treatment with CPTH6 [17] was evaluated by detecting CD31-positive cells in 5 μm paraffin sections by a streptavidin-biotin enhanced immunoperoxidase technique in an automated autostainer (BondTM Max, Leica BioSystem).…”