Clinical implications of microRNAs in cancer

Abstract

MicroRNAs (miRNAs) are endogenously produced non-coding RNAs that serve as micromanagers by negatively regulating gene expression. MiRNAs are implicated in several biological pathways including development of neoplasia. Because altered miRNA expression is implicated in the pathobiology of various cancers, these molecules serve as potential therapeutic targets. Using miRNA mimics to restore levels of aberrantly down-regulated miRNAs or miRNA inhibitors to inactivate over-expressed miRNAs shows promise as the next generation of therapeutic strategies. Manipulation of miRNAs offers an alternative therapeutic approach for chemo- and radiation-resistant tumors. Similarly, miRNA expression patterns can be used for diagnosis and to predict prognosis and efficacy of therapy. We present here an overview of how miRNAs affect cancers, how they may be used as biomarkers, and the clinical implications of miRNAs in cancer.     

Physiological mechanisms and movement analysis in Parkinson's disease

We present new ideas about motor control in the human central nervous system and about pathophysiological mechanisms of Parkinson's disease, and we describe the Posturo-Locomotion-Manual (PLM) method, which is a new technique utilizing optoelectronic camera recording for objective, fully quantitative, and standardized assessment of human motor performance. In the PLM test, recordings of body movements are made during a simple motor task, where the subject repeatedly moves a small object from its starting position on the floor to a shelf located at chin height a few steps forward. The duration of the postural (raising up), locomotor and the goal-directed manual phase of the forward directed body movement is automatically calculated by a small computer as well as the degree of coordination (simultaneity) of these phases. The technique has high resolution and has been used for clinical assessment of motor performance, drug testing, and so on, in neurological and geriatric practice.     

Apolipoprotein A-V is a potential target for treating coronary artery disease: evidence from genetic and metabolomic analyses

Triglyceride (TG)-lowering LPL variants in combination with genetic LDL-C-lowering variants are associated with reduced risk of coronary artery disease (CAD). Genetic variation in the APOA5 gene encoding apolipoprotein A-V also strongly affects TG levels, but the potential clinical impact and underlying mechanisms are yet to be resolved. Here, we aimed to study the effects of APOA5 genetic variation on CAD risk and plasma lipoproteins through factorial genetic association analyses. Using data from 309,780 European-ancestry participants from the UK Biobank, we evaluated the effects of lower TG levels as a result of genetic variation in APOA5 and/or LPL on CAD risk with or without a background of reduced LDL-C. Next, we compared lower TG levels via APOA5 and LPL variation with over 100 lipoprotein measurements in a combined sample from the Netherlands Epidemiology of Obesity study (N = 4,838) and the Oxford Biobank (N = 6,999). We found that lower TG levels due to combined APOA5 and LPL variation and genetically-influenced lower LDL-C levels afforded the largest reduction in CAD risk (odds ratio: 0.78 (0.73–0.82)). Compared to patients with genetically-influenced lower TG via LPL, genetically-influenced lower TG via APOA5 had similar and independent, but notably larger, effects on the lipoprotein profile. Our results suggest that lower TG levels as a result of APOA5 variation have strong beneficial effects on CAD risk and the lipoprotein profile, which suggest apo A-V may be a potential novel therapeutic target for CAD prevention.     

Pursuit of proteomic excellence and the excitement in Košice,Slovakia, at the 11th Central and Eastern European Proteomic Conference (CEEPC)

The Central and Eastern European Proteomic Conference (CEEPC) successfully launched its second decade of proteomics in Ko?ice, Slovakia with a program of systems biology, cellular, clinical, veterinary and sports proteomics. Whilst many conferences are struggling to attract participants, CEEPC with its outstanding track record and unique ‘family – feel’ packaged with excellent ambiance is thriving and bringing together proteomics experts from academia, industry, scientific specialties, clinics and precision medicine communities interested in resolving mysteries about protein functionalities in health and disease. CEEPC is also renowned for addressing humanitarian global healthcare issues, may it be ageing, chronic diseases or global epidemics. This year CEEPC intertwined with Ko?ice Peace Marathon’s pursuit of excellence in sports and initiatives including sports medicine and global peace.     

Downregulation of microRNA‐15a‐3p is correlated with clinical outcome and negatively regulates cancer proliferation and migration in human osteosarcoma

In this study, we investigated the expression, correlation to clinical outcomes and biological functions of microRNA‐15a‐3p (miR‐15a‐3p) in human osteosarcoma. MiR‐15a‐3p expressions in osteosarcoma cell lines and clinical tissues of osteosarcoma patients were measured by qPCR. Relevance of endogenous miR‐15a‐3p to osteosarcoma patients' clinicopathological factors or overall survival was statistically analyzed. In addition, the independence of miR‐15a‐3p predicting cancer patients' overall survival was analyzed by Cox regression method. Furthermore, in osteosarcoma cell lines, Saos‐2 and HOS cells, miR‐15a‐3p was overexpressed through stable lentiviral transduction. The functional regulations of miR‐15a‐3p overexpression on cancer ell proliferation and migration were then analyzed. MiR‐15a‐3p was significantly downregulated in osteosarcoma cell lines and human osteosarcoma tumors. Downregulation of endogenous miR‐15a‐3p in osteosarcoma tumors was significantly associated with cancer patient's poor clinical outcomes and low survival rate. Also, endogenous miR‐15a‐3p was confirmed to be an independent biomarker for predicating cancer patients' survival. In Saos‐2 and HOS cells, lentivirus‐induced miR‐15a‐3p overexpression had significantly tumor suppressing functions, by inhibiting both proliferation and migration. Significant downregulation of miR‐15a‐3p in osteosarcoma may be an independent biomarker to predicting cancer patients' poor prognosis. Overexpression miR‐15a‐3p may be an efficient functional meaning to suppress osteosarcoma development.     

Influence of a dosing-time on toxicities induced by docetaxel,cisplatin and 5-fluorouracil in patients with oral squamous cell carcinoma; a cross-over pilot study

Docetaxel, cisplatin plus fluorouracil (DCF) regimen is a useful chemotherapy, but is sometimes withdrawn due to severe adverse effects (AE). In this study, we examined whether the chronotherapy of DCF regimen could reduce the drugs-induced toxicities in clinical practice. Patients with oral squamous cell carcinoma were enrolled. Chemotherapy started at 10:30 (Morning-dosing) or 18:30 (Evening-dosing) for 5 days by a cross-over design. AE were assessed for 14 days after an initiation of each dosing. The grades of nausea, vomiting and neutropenia were smaller during Evening-dosing than during Morning-dosing. These data suggest that the chrono-chemotherapy might provide a merit for reducing the DCF regimen-related severe AE.