29 research outputs found

    Additional file 11: of SWATH-MS based quantitative proteomics analysis reveals that curcumin alters the metabolic enzyme profile of CML cells by affecting the activity of miR-22/IPO7/HIF-1Îą axis

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    Figure S6. IPO7/miRNAs correlation. a Analysis performed by using microRNA target prediction software miRSearch V3.0 showed that IPO7 is a validated target of miR-22 and miR-9. b Analysis of predicted multiple targets performed by MicroRNA Target prediction (miRTar) tool ( http://mirtar.mbc.nctu.edu.tw/human/ ) revealed within the CurcuDown-Regulated dataset the presence of several of miR-22 targets beside IPO7. No target of miR-9 was found. (PPTX 179 kb

    Table1_Long non-coding RNA H19 enhances the pro-apoptotic activity of ITF2357 (a histone deacetylase inhibitor) in colorectal cancer cells.DOCX

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    Introduction: Long non-coding RNA H19 (lncH19) is highly expressed in colorectal cancer (CRC) and plays critical roles in tumor development, proliferation, metastasis, and drug resistance. Indeed, the expression of lncH19 usually affects the outcomes of chemo-, endocrine, and targeted therapies. ITF2357 (givinostat) is a histone deacetylase inhibitor (HDACi) that revealed a significant anti-tumor action by inducing apoptosis in different tumor models, including leukemia, melanoma, and glioblastoma. However, no data are present in the literature regarding the use of this compound for CRC treatment. Here, we investigate the role of lncH19 in ITF2357-induced apoptosis in CRC cells.Methods: The HCT-116 CRC cell line was stably silenced for H19 to investigate the role of this lncRNA in ITF2357-induced cell death. Cell viability assays and flow cytometric analyses were performed to assess the anti-proliferative and pro-apoptotic effects of ITF2357 in CRC cell lines that are silenced or not for lncH19. RT-PCR and Western blot were used to study the effects of ITF2357 on autophagy and apoptosis markers. Finally, bioinformatics analyses were used to identify miRNAs targeting pro-apoptotic factors that can be sponged by lncH19.Results: ITF2357 increased the expression levels of H19 and reduced HCT-116 cell viability, inducing apoptosis, as demonstrated by the increase in annexin-V positivity, caspase 3 cleavage, and poly (ADP-ribose) polymerase (PARP-1) degradation. Interestingly, the apoptotic effect of ITF2357 was much less evident in lncH19-silenced cells. We showed that lncH19 plays a functional role in the pro-apoptotic activity of the drug by stabilizing TP53 and its transcriptional targets, NOXA and PUMA. ITF2357 also induced autophagy in CRC cells, which was interpreted as a pro-survival response not correlated with lncH19 expression. Furthermore, ITF2357 induced apoptosis in 5-fluorouracil-resistant HCT-116 cells that express high levels of lncH19.Conclusion: This study shows that lncH19 expression contributes to ITF2357-induced apoptosis by stabilizing TP53. Overall, we suggest that lncH19 expression may be exploited to favor HDACi-induced cell death and overcome 5-fluorouracil chemoresistance.</p

    Effects of CTO on cell adhesion molecules and cytokines mRNA expression.

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    <p>(I) CTO reverts the effects of CML exosome treatment on VCAM1, ICAM1 and IL8 mRNA expression in HUVEC cells. VCAM1 (a), ICAM1(b) and IL8 (c) mRNA expression increased in a dose dependent manner after adding exosomes (Exo) to endothelial cell monolayer. CTO (1-5-10 µM) reverts these effects in a time- and dose dependent manner. (II) VCAM1, ICAM1 and IL8 mRNA expression in HUVEC treated for 6 h either with low serum medium (CN), or with 50 µg/ml exosomes (Exo), or with 10 ng/ml of recombinant IL8 (Rec IL8) with or without CTO 10 µM, or with 50 µg/ml exosomes plus 10 µg/ml of a neutralizing anti-IL8 antibody (N Ab IL8). Values are representative for three independent experiments. *p≤0.05; **p≤0.01.</p

    CTO inhibits the effects of LAMA84R exosomes on HUVEC migration.

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    <p>(a) Effects on migration of CTO-treated endothelial cells using 50 µg/ml of exosomes as chemoattractant. (b) 50 µg/ml of exosomes (Exo) with or without 10 µg/ml of neutralizing anti-IL8 antibody (N Ab IL8), or 10 ng/ml of recombinant IL8 (Rec IL8) with or without neutralizing anti-IL8 antibody were added as chemoattractants to the bottom wells., Motility of endothelial cells with or without increasing doses of CTO (1–10 µM) was evaluated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042310#s2" target="_blank">Material and Methods</a>. *p≤0.05; **p≤0.01.</p