Tumor Suppressor miRNA in Cancer Cells and the Tumor Microenvironment: Mechanism of Deregulation and Clinical Implications

MicroRNAs (miRNAs) are noncoding RNAs that have been identified as important posttranscriptional regulators of gene expression. miRNAs production is controlled at multiple levels, including transcriptional and posttranscriptional regulation. Extensive profiling studies have shown that the regulation of mature miRNAs expression plays a causal role in cancer development and progression. miRNAs have been identified to act as tumor suppressors (TS) or as oncogenes based on their modulating effect on the expression of their target genes. Upregulation of oncogenic miRNAs blocks TS genes and leads to tumor formation. In contrast, downregulation of miRNAs with TS function increases the translation of oncogenes. Several miRNAs exhibiting TS properties have been studied. In this review we focus on recent studies on the role of TS miRNAs in cancer cells and the tumor microenvironment (TME). Furthermore, we discuss how TS miRNA impacts the aggressiveness of cancer cells, with focus of the mechanism that regulate its expression. The study of the mechanisms of miRNA regulation in cancer cells and the TME may paved the way to understand its critical role in the development and progression of cancer and is likely to have important clinical implications in a near future. Finally, the potential roles of miRNAs as specific biomarkers for the diagnosis and the prognosis of cancer and the replacement of tumor suppressive miRNAs using miRNA mimics could be promising approaches for cancer therapy.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Acute myeloid leukemia-derived exosomes deliver miR-24-3p to hinder the T-cell immune response through DENN/MADD targeting in the NF-κB signaling pathways

Abstract Background microRNAs (miRNAs) are known as potent gene expression regulators, and several studies have revealed the prognostic value of miRNAs in acute myeloid leukemia (AML) patient survival. Recently, strong evidence has indicated that miRNAs can be transported by exosomes (EXOs) from cancer cells to recipient immune microenvironment (IME) cells. Results We found that AML blast-released EXOs enhance CD3 T-cell apoptosis in both CD4 and CD8 T cells. We hypothesized that miRNAs present in EXOs are key players in mediating the changes observed in AML T-cell survival. We found that miR-24-3p, a commonly overexpressed miRNA in AML, was present in released EXOs, suggesting that EXO-miR-24-3p was linked to the increased miR-24-3p levels detected in isolated AML T cells. These results were corroborated by ex vivo-generated miR-24-3p-enriched EXOs, which showed that miR-24-3p-EXOs increased apoptosis and miR-24-3p levels in T cells. We also demonstrated that overexpression of miR-24-3p increased T-cell apoptosis and affected T-cell proliferation by directly targeting DENN/MADD expression and indirectly altering the NF-κB, p-JAK/STAT, and p-ERK signaling pathways but promoting regulatory T-cell (Treg) development. Conclusions These results highlight a mechanism through which AML blasts indirectly impede T-cell function via transferred exosomal miR-24-3p. In conclusion, by characterizing the signaling network regulated by individual miRNAs in the leukemic IME, we aimed to discover new nonleukemic immune targets to rescue the potent antitumor function of T cells against AML blasts. Video Abstrac

Global MPP Tracking for Photovoltaic Panel under Shading Conditions using Robust Numerical Algorithm

This paper presents a new numerical approach for the modelling of the PV panels under partial shading conditions. It also solves the major drawback of the PV systems, which is the tracking of maximum power point under partial shading conditions where the P-V characteristic has a more complex structure with many local maximums on the graph. This paper aims to resolve this phenomenon using Newton method in order to find the global maximum power point

The Effect of Lymph Nodes’ Histologic Response on Survival Outcomes in Moroccan Patients with Rectal Cancer

Prognosis for patients with locally advanced rectal cancer remains controversial. The purpose of this study was to elucidate possible association between therapeutic effect on lymph nodes (LNs) and patient prognosis. Overall, 149 patients with rectal cancer received preoperative radiotherapy in concomitance with chemotherapy or exclusive radiotherapy before rectal excision. Microscopic examination of formalin-fixed lymph nodes was assessed for therapeutic effect. The establishment of groups combined reaction tissue types of fibrosis, colloid, and necrosis after neoadjuvant treatment was assigned. The average age was 56.38 years, ranged between 22 and 88 years, 53% were female, and 47% were men, with a sex ratio of 1 : 12. In the present study, we noticed that after a median follow-up time of 40.67 months (0–83; SD: 21.1), overall survival was statistically significant depending on age groups. Kaplan–Meier analysis showed significant differences in the rate of patients with an age under 65 years (70.64%) versus those with an age over 85 years (36.5%) (p<0.001). Also, the OS was statistically significant depending on therapeutic effect groups composed of 0TE (No Therapeutic effect), C+ (presence of only colloidal effect), F+ (presence of only fibrosis tissue), and ME+ (mixture of 2 or 3 types of therapeutic effect) group. Indeed, we observed a significantly higher OS rate in the ME + group (86%) compared with the OS rate of LNs group with no therapeutic effect (57%) (p=0.028). Additionally, there was a significant association between the presence of fibrosis on LNs and an extended delay of more than 8 weeks to neoadjuvant treatment completion and surgery. Our study indicates that the best patient prognosis could be predicted based on tumor presenting a best pathologic effect on lymph nodes, and that delaying surgery for more than 8 weeks to neoadjuvant treatment completion improves therapeutic response on LNs

Study of the corrosion inhibition of C38 steel in a 1M HCl medium by the etanoic extract of Rumex Nervosus Vahl leaves

The efficacy of Rumex Nervosus Vahl Leaves Ethanolic extract (RNVLE) to inhibit C38 steel corrosion in one molar hydrochloric acid medium was examined using electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization. Polarization measurements revealed mixed-type inhibitor behavior. The inhibitory efficacy assessed by both polarization and (EIS) techniques was consistent, with an IE value of (96.0 %) and (95.5 %) at 2g/L of RNVLE, respectively. The RNVLE adsorption on the C38 metal surfaces in 1M HCl follows the Langmuir adsorption isotherm. The calculated free energy (G°ads equal to -16.1 KJ mol-1) explained that RNVLE controls the corrosion process by physisorption. The effect of immersion time was also investigated. This study demonstrated that RNVLE can be considered an excellent inhibitor up to 6 hours and after this time; it is considered a lower quality inhibitor although it still has sufficient inhibitory ability. SEM-EDX (Scanning Electron Microscopy and X-ray Energy Dispersive Spectroscopy) analysis revealed that the extract molecules adsorb on the metal's surface. These findings indicate that RNVLE can be used as an effective corrosion inhibitor for C38 steel in 1M HCl solution