MicroRNAs (miRNAs) are small non-coding RNAs that can modulate mRNA expression. Insights into the roles of miRNAs in development and disease have led to the development of new therapeutic approaches that are based on miRNA mimics or agents that inhibit their functions (antimiRs), and the first such approaches have entered the clinic. This Review discusses the role of different miRNAs in cancer and other diseases, and provides an overview of current miRNA therapeutics in the clinic. In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development. Several miRNA-targeted therapeutics have reached clinical development, including a mimic of the tumour suppressor miRNA miR-34, which reached phase I clinical trials for treating cancer, and antimiRs targeted at miR-122, which reached phase II trials for treating hepatitis. In this article, we describe recent advances in our understanding of miRNAs in cancer and in other diseases and provide an overview of current miRNA therapeutics in the clinic. We also discuss the challenge of identifying the most efficacious therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics.

MicroRNA therapeutics: towards a new era for the management of cancer and other diseases

MicroRNAs (miRNAs) are critical regulators of gene expression. Amplification and overexpression of individual 'oncomiRs' or genetic loss of tumour suppressor miRNAs are associated with human cancer and are sufficient to drive tumorigenesis in mouse models. Furthermore, global miRNA depletion caused by genetic and epigenetic alterations in components of the miRNA biogenesis machinery is oncogenic. This, together with the recent identification of novel miRNA regulatory factors and pathways, highlights the importance of miRNA dysregulation in cancer.

MicroRNA biogenesis pathways in cancer

Due to the comprehensive examination of 50 patients with ovarian polycystosis the authors suggested that ultrasound, laparoscopic, hormonal and endometrial parameters should be employed as diagnostic criteria.

Diagnostic criteria for polycystic ovary syndrome

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

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Biomarkers of Nutrition for Development (BOND)-Iron Review.

At-a-glance The kynurenine pathway is the main pathway for tryptophan metabolism. It generates compounds that can modulate activity at glutamate receptors and possibly nicotinic receptors, in addition to some as-yet-unidentified sites. The pathway is in a unique position to regulate other aspects of the metabolism of tryptophan to neuroactive compounds, and also seems to be a key factor in the communication between the nervous and immune systems. It also has potentially important roles in the regulation of cell proliferation and tissue function in the periphery. As a result, the pathway presents a multitude of potential sites for drug discovery in neuroscience, oncology and visceral pathology.

Endogenous kynurenines as targets for drug discovery and development

Cytokines and anticytokines in psoriasis

The aim of our study was to define tissue and plasma miRNA signatures, which could potentially serve as diagnostic and prognostic markers in endometrioid endometrial cancer (EEC) and to investigate miRNA profiles in regard to clinicopathological characteristics. Tissue and plasma samples were collected from 122 women (77 EEC and 45 controls). Expression profiling of 866 human miRNAs and 89 human viral miRNAs was performed in 24 samples and was followed by qPCR validation in 104 patients. Expression of 16 miRNAs was analyzed in 48 plasma samples. Microarray study revealed regulation of 21 miRNAs in EEC tissues comparing to normal endometrium. Altered expression of 17 miRNAs was confirmed by qPCR performed in 104 tissue samples. Seven miRNAs were upregulated and two were downregulated in EEC plasma samples. Expression of a number of miRNAs was associated with International Federation of Gynecology and Obstetrics stage, grade, relapse and nodal metastases. Two miRNA signatures: miR-92a/miR-410 and miR-92a/miR-205/miR-410 classified tumor tissues with higher accuracy in comparison to single miRNAs (AUC: 0.977, 95% CI: 0.927-0.996 and 0.984, 95% CI: 0.938-0.999, respectively). miRNA signature composed of miR-205 and miR-200a predicted relapse with AUC of 0.854 (95% CI: 0.691-0.951). Tissue miRNA signatures were independent prognostic markers of overall (miR-1228/miR-200c/miR-429, HR: 2.98) and progression-free survival (miR-1228/miR-429, HR: 2.453). Plasma miRNA signatures: miR-9/miR-1228 and miR-9/miR-92a, classified EEC plasma samples with high accuracy yielding AUCs of 0.909 (95% CI: 0.789-973) and 0.913 (95% CI: 0.794-0.976), respectively. We conclude that miRNA signatures hold a great promise to become noninvasive biomarkers for early EEC detection and prognosis.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.27840

Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients.

Alterations of mTOR gene expression have been implicated in the pathogenesis of endometrioid endometrial cancer however only few studies explored the cause of increased mTOR activation in this malignancy. miRNAs are small, noncoding RNAs, which were proven to regulated gene expression at the posttranscriptional level. The study aimed to explore deregulation of miRNAs targeting mTOR kinase (miR-99a, miR-100 and miR-199b) as a possible cause of its altered expression in EEC tissues. In addition expression of the three miRNAs was investigated in plasma of EEC patients and was assessed in terms of diagnostic and prognostic utility.

/pdf/deregulation-of-mir-100-mir-99a-and-mir-199b-in-tissues-and-2fvko65z99.pdf

Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma

Psoriasis is a chronic genetically determined, erythemato-squamous disease associated with many comorbidities. Evidence from clinical studies and experimental models support the concept that psoriasis is a T cell-mediated inflammatory skin disease and T helper (Th) cells – Th1, Th17 and Th22 – play an important role in the pathogenesis. Th1 cytokines IFNγ, IL-2, as well as Th17 cytokines IL-17A, IL-17F, IL-22, IL-26, and TNFα (Th1 and Th17 cytokine) are increased in serum and lesional skin. IL-22 produced by Th17 and new subset of T helper cells, Th22, is also increased within psoriatic lesions and in the serum. Other recently recognized cytokines of significant importance in psoriasis are IL-23, IL-20 and IL-15. The IL-23/Th17 pathway plays a dominant role in psoriasis pathogenesis. Currently due to enormous methodological progress, more and more clinical and histopathological psoriatic features could be explained by particular cytokine imbalance, which still is one of the most fascinating dermatological research fields stimulating new and new generations of researchers.

Cytokine network in psoriasis revisited

Despite the efforts to decrease the rate of preterm birth, preterm delivery is still the main cause of neonatal morbidity and mortality. Identifying patients threatened with preterm delivery remains one of the main obstetric challenges. The aim of this study was to estimate the potential value of elastographic evaluation of internal cervical os stiffness at 18-22 weeks of pregnancy in low risk, asymptomatic women in the prediction of spontaneous preterm delivery. This prospective observational study included 333 low-risk, asymptomatic women presenting for the routine second trimester ultrasound scan according to the Polish Gynecological Society recommendation between 18-22 weeks of pregnancy. Ultrasound examinations of the cervix were performed transvaginally. The following data were recorded: elastographic color assessment of the internal os and ultrasound cervical length at 18-22 and 30 weeks of pregnancy; maternal age; obstetrical history; presence of cervical funneling at 30 weeks of pregnancy; gestational age at birth. Elastographic assessment of the internal os was performed using a color map: red (soft), yellow (medium soft), blue (medium hard) and purple (hard). If two colors were visible in the region of the internal os, the softer option was noted. Statistical analysis was performed using Statistica software (version 10, Statsoft Poland) using the following tests: chi square test to compare frequency of preterm deliveries in various categories of internal os assessment and Spearman correlation test to determine the correlation between elastographic assessment and cervical shortening. To determine the cut off category of internal os elastography assessment in selecting high preterm delivery risk patients we have calculated the sensivity, specifity, negative predictive value and positive predictive value. The number of preterm deliveries (<37 weeks of pregnancy) was significantly higher in the red and yellow groups, than in the blue and purple groups. The sensivity, specifity, NPV and PPV for both red and yellow internal os assessment in predicting preterm delivery were 85.7%, 97.6%, 98.3% and 81.1% respectively. Elastographic assessment of the internal cervical os at 18-22 weeks of pregnancy may identify patients with high risk of preterm delivery in low-risk, asymptomatic women.

https://link.springer.com/content/pdf/10.1186%2F1471-2393-14-238.pdf

Tomasz Paszkowski

Papers

Cytokines and anticytokines in psoriasis

Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients.

Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma

Cytokine network in psoriasis revisited

Elastography in predicting preterm delivery in asymptomatic, low-risk women: a prospective observational study.