microRNAs (miRNAs) are small noncoding endogenously produced RNAs that play key roles in controlling the expression of many cellular proteins. Once they are recruited and incorporated into a ribonucleoprotein complex miRISC, they can target specific mRNAs in a miRNA sequence-dependent process and interfere in the translation into proteins of the targeted mRNAs via several mechanisms. Consequently, miRNAs can regulate many cellular pathways and processes. Dysregulation of their physiological roles may largely contribute to disease. In particular, in cancer, miRNAs can be involved in the deregulation of the expression of important genes that play key roles in tumorigenesis, tumor development, and angiogenesis and have oncogenic or tumor suppressor roles. This review focuses on the biogenesis and maturation of miRNAs, their mechanisms of gene regulation, and the way their expression is deregulated in cancer. The involvement of miRNAs in several oncogenic pathways such as angiogenesis and apoptosis, and in the inter-cellular dialog mediated by miRNA-loaded exosomes as well as the development of new therapeutical strategies based on miRNAs will be discussed.
Gliomas such as oligodendrogliomas (ODG) and glioblastomas (GBM) are brain tumours with different clinical outcomes. Histology-based classification of these tumour types is often difficult. Therefore the first aim of this study was to gain microRNA data that can be used as reliable signatures of oligodendrogliomas and glioblastomas. We investigated the levels of 282 microRNAs using membrane-array hybridisation and real-time PCR in ODG, GBM and control brain tissues. In comparison to these control tissues, 26 deregulated microRNAs were identified in tumours and the tissue levels of seven microRNAs (miR-21, miR-128, miR-132, miR-134, miR-155, miR-210 and miR-409-5p) appropriately discriminated oligodendrogliomas from glioblastomas. Genomic, epigenomic and host gene expression studies were conducted to investigate the mechanisms involved in these deregulations. Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs. We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression. Moreover, MDH1, the target of several deregulated microRNAs, is repressed in glioblastomas, making an intramitochondrial-NAD reduction mediated by the mitochondrial aspartate-malate shuttle unlikely. Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.
BackgroundHIV infection is an emerging problem in Laos. We conducted the first prospective study on intestinal parasites, including opportunistic protozoa, in newly diagnosed HIV infected patients, with or without diarrhea. The aims were to describe the spectrum of infections, to determine their prevalence and to assess their associations with diarrhea, CD4 cell count, place of residence and living conditions.MethodologyOne to three stool samples over consecutive days were obtained from 137 patients. The Kato thick smear method, formalin-ethyl concentration and specific stains for coccidia and microsporidia diagnosis were performed on 260 stool samples. Baseline characteristics regarding relevant demographics, place of residence and living conditions, clinical features including diarrhea, were collected using a standardized questionnaire.Principal FindingsThe 137 patients were young (median age: 36 years) and severely immunocompromised (83.9% at WHO stage 3 or 4, median CD4 cell count: 41/mm3). Diarrhea was present in 43.0% of patients. Parasite infection was found in 78.8% of patients, infection with at least two species in 49.6%. Prevalence rates of protozoan and helminth infections were similar (54.7% and 58.4% respectively). Blastocystis sp. was the most frequent protozoa (26.3%). Cryptosporidium sp., Cytoisospora belli and microsporidia, found at low prevalence rates (6.6%, 4.4%, 2.9%, respectively), were described for the first time in Laos. Cryptosporidium sp. was associated with persistent diarrhea. Strongyloides stercoralis was the most prevalent helminth following Opisthorchis viverrini (20.4% and 47.5% respectively). The most immunocompromised patients, as assessed by a CD4 count ≤ 50 cells/mm3, were more likely to be infected with intestinal parasites.Conclusions/SignificanceHIV infection was mainly diagnosed at an advanced stage of immunosuppression in Lao patients. Intestinal parasite infections were highly prevalent regardless of their diarrheal status. Opportunistic infections were reported. Improving the laboratory diagnosis of intestinal parasite infections and the knowledge on their local risk factors is warranted.
Abstract.Tumor invasion or infiltration of adjacent tissues is the source of clinical challenges in diagnosis as well as prevention and treatment. Among brain tumors, infiltration of the adjacent tissues with diverse pleiotropic mechanisms is frequently encountered in benign meningiomas. We assessed whether a multiparametric analysis of meningiomas based on data from both clinical observations and molecular analyses could provide a consistent and accurate appraisal of invasive and infiltrative phenotypes and help determine the diagnosis of these tumors. Tissue analyses of 37 meningiomas combined enzyme-linked immunosorbent assay (ELISA) and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) assays of two different protein biomarkers (thrombospondin 1 and a phosphorylated form of vimentin) as well as gene expression analyses with oligonucleotide microarrays. Up to four different clinical and molecular parameters were then examined for tumor classification. From this study, we were able to cluster 36 out of the 37 tumors into two different subsets corresponding to infiltrative/invasive and non-infiltrative tumors. In addition, meningiomas that invade brain and those that infiltrate the neighboring skull bone exhibited no distinguishable molecular features. Our multiparameter analysis that combines clinical data, transcriptomic and molecular assays clearly reveals the heterogeneity of meningiomas and distinguishes the intrinsically infiltrative/invasive tumors from the non-infiltrative meningiomas.
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