J. Clin. Med., Volume 4, Issue 8 (August 2015) – 8 articles , Pages 1536-1667

MicroRNAs (miRNAs) are short non-coding RNAs of 20 to 25 nucleotides that regulate gene expression post-transcriptionally mainly by binding to a specific sequence of the 3′ end of the untranslated region (3′UTR) of target genes. Since the first report on the clinical relevance of miRNAs in cancer, many miRNAs have been demonstrated to act as oncogenes, whereas others function as tumor suppressors. Furthermore, global miRNA dysregulation, due to alterations in miRNA processing factors, has been observed in a large variety of human cancer types. As previous studies have shown, the sequential miRNA processing can be divided into three steps: processing by RNAse in the nucleus; transportation by Exportin-5 (XPO5) from the nucleus; and processing by the RNA-induced silencing complex (RISC) in the cytoplasm. Alteration in miRNA processing genes, by genomic mutations, aberrant expression or other means, could significantly affect cancer initiation, progression and metastasis. In this review, we focus on the biogenesis of miRNAs with emphasis on the potential of miRNA processing factors in human cancers. Full article

The discovery of small non-coding RNAs known as microRNAs has refined our view of the complexity of gene expression regulation. In hepatocellular carcinoma (HCC), the fifth most frequent cancer and the third leading cause of cancer death worldwide, dysregulation of microRNAs has been implicated in all aspects of hepatocarcinogenesis. In addition, alterations of microRNA expression have also been reported in non-cancerous liver diseases including chronic hepatitis and liver cirrhosis. MicroRNAs have been proposed as clinically useful diagnostic biomarkers to differentiate HCC from different liver pathologies and healthy controls. Unique patterns of microRNA expression have also been implicated as biomarkers for prognosis as well as to predict and monitor therapeutic responses in HCC. Since dysregulation has been detected in various specimens including primary liver cancer tissues, serum, plasma, and urine, microRNAs represent novel non-invasive markers for HCC screening and predicting therapeutic responses. However, despite a significant number of studies, a consensus on which microRNA panels, sample types, and methodologies for microRNA expression analysis have to be used has not yet been established. This review focuses on potential values, benefits, and limitations of microRNAs as new clinical markers for diagnosis, prognosis, prediction, and therapeutic monitoring in HCC. Full article

The growing attention that non-coding RNAs have attracted in the field of cancer research in recent years is undeniable. Whether investigated as prospective therapeutic targets or prognostic indicators or diagnostic biomarkers, the clinical relevance of these molecules is starting to emerge. In addition, identification of non-coding RNAs in a plethora of body fluids has further positioned these molecules as attractive non-invasive biomarkers. This review will first provide an overview of the synthetic cascade that leads to the production of the small non-coding RNAs microRNAs (miRNAs) and presents their strengths as biomarkers of disease. Our interest will next be directed at exploring the diagnostic utility of miRNAs in two types of cancer: the brain tumor glioblastoma multiforme (GBM) and breast cancer. Finally, we will discuss additional clinical implications associated with miRNA detection as well as introduce other non-coding RNAs that have generated recent interest in the cancer research community. Full article

Hepatocellular carcinoma (HCC) is a poor-prognosis cancer due to its high rate of recurrence. microRNAs (miRNAs) are a class of small non-coding RNA molecules that affect crucial processes in cancer development. The objective of this study is to identify the role of miRNAs in patient bone marrow (BM) and explore the function of these molecules during HCC progression. We purified miRNAs from bone marrow cells of seven HCC patients, and divided them into three fractions by cell surface markers as follows: CD14⁺ (macrophage), CD14⁻/CD45⁺ (lymphocyte), and CD14⁻/CD45⁻/EpCAM⁺ (epithelial cell). We employed microarray-based profiling to analyze miRNA expression in the bone marrow of patients with HCC. Differentially expressed miRNAs were significantly different between fractions from whole bone marrow, macrophages, and lymphocytes, and depended on stages in tumor progression. Differences in expression of miRNAs associated with cell proliferation also varied significantly between HCC patients with recurrence, multiple tumors, and advanced clinical stages. These results suggest that miRNA profiles in separated fractions of BM cells are associated with HCC progression. Full article

Tumor progression requires cancer cell proliferation, migration, invasion, and attraction of blood and lymph vessels. These processes are tightly regulated by growth factors and their intracellular signaling pathways, which culminate in transcriptional programs. Hence, oncogenic mutations often capture growth factor signaling, and drugs able to intercept the underlying biochemical routes might retard cancer spread. Along with messenger RNAs, microRNAs play regulatory roles in growth factor signaling and in tumor progression. Because growth factors regulate abundance of certain microRNAs and the latter modulate the abundance of proteins necessary for growth factor signaling, the two classes of molecules form a dense web of interactions, which are dominated by a few recurring modules. We review specific examples of the alliance formed by growth factors and microRNAs and refer primarily to the epidermal growth factor (EGF) pathway. Clinical applications of the crosstalk between microRNAs and growth factors are described, including relevance to cancer therapy and to emergence of resistance to specific drugs. Full article

MiR-221 and miR-222 (miR-221/222) are well-studied oncogenic microRNAs that are frequently upregulated in several types of human tumors, such as esophageal adenocarcinoma, gastric adenocarcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma. In these cancers, silencing miR-221/222 could represent a novel anti-tumor approach to inhibit tumor growth and metastasis. On the other hand, miR-221/222 also play onco-suppressive roles in cholangiocarcinoma and gastrointestinal stromal tumors (GISTs). Here we will review the roles of miR-221/222 in digestive systems and their possibility as prognostic and therapeutic tools. Full article

Ethnicity and race are often used interchangeably in the literature. However, the traditional definition of race and ethnicity is related to biological (bone structure and skin, hair, or eye color) and sociological factors (nationality, regional culture, ancestry, and language) respectively. Diabetes mellitus (DM) is a huge global public health problem. As the number of individuals with Type 2 DM grows, the prevalence of diabetic kidney disease (DKD), which is one of the most serious complications, is expected to rise sharply. Many ethnic and racial groups have a greater risk of developing DM and its associated macro and micro-vascular complications. Full article

Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. Full article