Role Of microRNAs In Development Research Articles

The Role of MicroRNAs in Development of Endometrial Cancer: A Literature Review.

Endometrial cancer (EC) ranks as the second most common gynaecological cancer worldwide. EC patients are diagnosed at an early clinical stage and generally have a good prognosis. Therefore, there is a dire need for development of a specific marker for early detection of endometrial adenocarcinoma. The development of EC is conditioned by a multistep process of oncogenic upregulation and tumor suppressor downregulation as shown by molecular genetic evidence. In this setting, microRNAs appear as significant regulators of gene expression and several variations in the expression of microRNAs have been implicated in normal endometrium, endometrial tissue, metrorrhagia, and endometrial cancer. Furthermore, microRNAs act as highly precise, sensitive, and robust molecules, making them potential markers for diagnosing specific cancers and their progression. With the rising incidence of EC, its management remains a vexing challenge and diagnostic methods for the disease are limited to invasive, expensive, and inaccurate tools. Therefore, the prospect of exploiting the utility of microRNAs as potential candidates for diagnosis and therapeutic use in EC seems promising.

The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer.

Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18–25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes’ expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment.

Profile of Judy Lieberman

“I am just hitting my stride,” says immunologist Judy Lieberman, while discussing her multiple research projects. The former high-energy theoretical physicist is now a chairperson of cellular and molecular medicine at Boston Children’s Hospital and a professor of pediatrics at Harvard Medical School. Elected to the National Academy of Sciences (NAS) in 2020, Lieberman is a pioneer in the therapeutic uses of RNA interference. She showed in an animal disease model that small RNAs can be used as a therapy and developed methods for delivering small RNAs selectively to particular cell types. Her achievements also include elucidating the molecular basis of killer lymphocyte cytotoxicity and identifying the role of microRNAs in development and cancer. Her Inaugural Article (1) reports a strategy for cancer immunotherapy that uses cancer cell-targeted gene knockdown to counteract the many ways tumor cells evade immune recognition. Judy Lieberman. Image credit: Judy Lieberman. Lieberman was born in Boston and raised in the New York City area. Her father was a businessman, while her mother was an elementary school teacher. She says, “I grew up in a very intellectual family, but not of scientists, although my uncle was a professor of biochemistry and member of the NAS. My parents were early feminists, who strongly believed that girls could do anything that boys could do.” The 1957 launch of Sputnik 1, the first artificial Earth satellite, heightened interest in science and led to expansion of youth educational programs. Lieberman benefited from this surge of interest while in high school, participating in a sciences and arts summer camp supported by the Ford Foundation, a Saturday science honors program at Columbia University, and a National Science Foundation (NSF) program in modern physics at Cornell University. “The NSF program turned me onto physics,” she says. After earning a bachelor’s degree summa cum …

The Role of MicroRNAs in Development and Function of Regulatory T Cells - Lessons for a Better Understanding of MicroRNA Biology.

MicroRNAs (miRNAs) have emerged as critical posttranscriptional regulators of the immune system, including function and development of regulatory T (Treg) cells. Although this critical role has been firmly demonstrated through genetic models, key mechanisms of miRNA function in vivo remain elusive. Here, we review the role of miRNAs in Treg cell development and function. In particular, we focus on the question what the study of miRNAs in this context reveals about miRNA biology in general, including context-dependent function and the role of individual targets vs. complex co-targeting networks. In addition, we highlight potential technical pitfalls and state-of-the-art approaches to improve the mechanistic understanding of miRNA biology in a physiological context.

Роль микроРНК в развитии хронической обструктивной болезни легких

Роль микроРНК в развитии хронической обструктивной болезни легких

Role of microRNAs in breast cancer development and their potential as biomarkers

Breast cancer is the 2nd most common malignant disease after lung cancer; about 1 in 8 women will develop breast cancer in her lifetime. Cancer progression is a serious complication of the disease that encourages comprehensive investigation of molecular mechanisms underlying breast cancer development. This is also important for healthcare professionals involved in patient management, since they have to choose an optimal treatment regimen. This article discusses the role of microRNAs in the development of breast cancer, their biogenesis, classification, association with various molecular subtypes of breast cancer, and their potential role in the development of new targeted drugs for breast cancer therapy. Current research on the role of microRNAs in breast cancer progression is focused on the development of markers for breast cancer prognosis, diagnostic markers and new targeted drugs.

Role of microRNA in Development of Instability of Atherosclerotic Plaques.

MicroRNAs are small noncoding single-stranded RNAs that regulate gene expression. Today, we see an increasing number of studies highlighting the important role of microRNAs in the development and progression of cardiovascular diseases caused by atherosclerotic lesions of arteries. We review the available scientific data on association of the expression of these biomolecules with instability of atherosclerotic plaques in animal models and humans. We made special emphasis on miR-21, -100, -127, -133, -143/145, -221/222, and -494 because they were analyzed in more than one study. We discuss the possibility of microRNAs using in the diagnosis and therapy of atherosclerosis and its complications.

Role of MicroRNAs in Development of Immune Cells and Nervous System and their Relation to Multiple Sclerosis

Introduction: MicroRNAs (miRNAs) are small and non-coding ribonucleic acids that play critical roles in regulation of host genome expression at post-transcriptional level. An individual miRNA is able to down-regulate multiple targeted mRNA transcripts. Therefore, minor changes in a miRNA expression may lead to significant alterations in the expression of different genes. During last two decades, miRNAs have emerged as key regulators of immune cell lineage differentiation, maturation, maintenance of immune homeostasis, and normal function. Multiples sclerosis (MS) is a chronic inflammatory disease that is characterized by infiltration of lymphocytes into the central nervous system (CNS), demyelination and axonal degeneration. Although causes of MS are still unknown, it is widely accepted that novel drug targets need to focus on both decreasing inflammation and promoting CNS repair. Recent researches about MS disease have shown that miRNAs are dysregulated in the immune system and CNS, which shows their role in the MS pathogenesis. Conclusion: Identification of specific expression patterns of miRNA in autoimmune diseases and a further comprehensive understanding of their role in the pathogenesis of different diseases offers promise of not only novel molecular diagnostic markers but also new gene therapy strategies for treating inflammatory autoimmune diseases. In this study, we review the latest findings about miRNA biogenesis and signatures in the CNS and immune cells of MS patients.

From Cradle to the Grave: Tissue-specific microRNA signatures in detecting clinical progression of diabetes

Ever since the discovery of small non-coding RNAs, microRNAs have been identified to play a critical role in development and function of pancreatic insulin-producing beta cells. Research carried out until now demonstrates that microRNAs can specifically target key pancreatic transcription factors and signalling molecules. This in turn may influence changes in insulin production and secretion. microRNAs are also identified in insulin target organs that are altered as a result of hyperglycemia and insulin resistance. Recent studies demonstrate that microRNAs are not only confined to cells but are also detected in biological fluids including serum, plasma and urine. These data indicate that miRNAs may be looked upon having a dual role, as biomarkers and as regulators of disease. We review the existing literature in understanding the role of microRNAs in development, function and death of pancreatic beta cells as well as in the development of metabolic disease. We discuss the possible mechanisms that contribute to identifying the role of microRNAs as sensitive and efficient biomarkers to predict the progression of diabetes. Understanding tissue-specific microRNA signatures and their role as a cause or effect of diabetes would provide more information on progression of this disease.

MicroRNA-494 reduces DJ-1 expression and exacerbates neurodegeneration

Oxidative stress is believed to be a significant cause of Parkinson's disease (PD). DJ-1 is thought to be an oxidative sensor that protects cells from oxidative insult. It was reported that the level of total DJ-1 protein was significantly reduced in the substantia nigra of sporadic PD patients, suggesting that abnormal DJ-1 expression might contribute to PD pathogenesis. However, the molecular mechanisms underlying the regulation of DJ-1 expression are still not fully explored. As a post-transcriptional regulation of target gene expression, the roles of microRNAs in development and disease progression have received widespread concerns. Therefore, we hypothesized that microRNAs might participate in the regulation of the DJ-1 expression. In the present study, we found that miR-494 could bind to the 3′UTR of DJ-1. Overexpression of miR-494 significantly decreased the level of DJ-1 in vitro and rendered cells more susceptible to oxidative stress. In a MPTP mouse model, overexpression of miR-494 negatively regulated DJ-1 levels and exacerbated MPTP-induced neurodegeneration, as illustrated by the loss of dopaminergic neurons. In conclusion, upregulation of miR-494 contributed to oxidative stress induced neuronal death by inhibiting expression of DJ-1.

Discovery of prognostic factors for diagnosis and treatment of epithelial-derived ovarian cancer from laying hens.

Ovarian cancer is a lethal gynecological cancer causing cancer-related deaths in women worldwide. It is difficult to diagnosis at an early stage when more than 90% patients can be cured because of lack of specific symptoms and early detection markers. Most of malignant ovarian tumors are originated from the germinal epithelium of the ovary. For investigation with animal models of epithelial-derived ovarian cancer (EOC), laying hens are the most relevant animal models because they spontaneously develop EOC as occurs in women through ovulating almost every day. As in women, EOC in the hen is age-related and grossly and histologically similar to that in women. However, domesticated animals are inappropriate for research human EOC due to multiple pregnancies and lactating or seasonally anestrous. In addition, the non-spontaneous nature of rodents EOC limits clinical relevance with human EOC. Recent studies have shown that ovarian cancer could arise from epithelium from the oviduct as oviduct-related genes are up-regulated in EOC of hens. Therefore, we showed in the review: 1) characterization and classification of EOC; 2) chicken models for EOC; 3) relationship estrogen with EOC; 4) candidate prognostic factors for EOC including serpin peptidase inhibior, clade B (ovalbumin), member 3 (SERPINB3), SERPINB11, gallicin 11 (GAL11), secreted phosphoprotein 1 (SPP1) and alpha 2 macroglobulin (A2M) in normal and cancerous ovaries of laying hens; 5) biological roles of microRNAs in development of EOC. Collectively, the present reviews indicate that expression of SERPINB3, SERPINB11, GAL11, SPP1 and A2M is clearly associated with the development of ovarian carcinogenesis. These results provide new insights into the prognostic biomarkers for EOC to diagnose and to evaluate responses to therapies for treating EOC of humans.

The important role of microRNAs in development and diseases of nervous system

Background MicroRNAs (miRNAs) are a class of endogenous,small non-coding RNAs that mediate posttranscriptional gene silencing by complementary binding to the 3'untranslated region of target mRNAs.Accumulating evidences demonstrates that miRNAs regulate gene silencing in many signal pathways.Objective Review the role of miRNAs in the nervous system.Content The role of miRNAs in neuronal development,differentiation,as well as the pathological progression of neurodegenerative disease,the nervous system tumor and brain ischemia.Trend MicroRNAs have been ideal candidates for diagnosis,prognostic evaluation,preventing and curing disease. Key words: microRNA; Dicer; Neurodegeneration; Nervous system neoplasms

Role of microRNA in development and progression of glioblastoma

Glioblastoma,originating from glial cells,is the most commonly seen primary intracranial tumors in adults with extremely poor prognosis.miRNAs are a class of endogenous 18-26 nt non-coding RNAs playing important roles in a variety of biological processes.Recent studies have shown that miRNAs are closely associated with the development and progression of glioblastoma.In this paper,we summarize the regulatory roles of miRNAs in the progression of glioblastoma.

Abstract 2040: Identification of microRNAs associated with tamoxifen resistance in breast cancer

Abstract Tamoxifen is the most commonly used endocrine therapy for estrogen receptor-positive breast cancer patients. As an estrogen antagonist, tamoxifen competes for binding with estrogen receptor, thereby inhibiting estrogen-dependent gene transcription and tumor growth. However, some breast tumors become estrogen-independent and ultimately develop resistance to the treatment. The mechanisms underlying this transition in the control of cell proliferation remain unclear. Recent work has shown that aberrant expression of microRNAs has been frequently detected in breast cancer and some of which are associated with breast cancer metastasis, poor prognosis, suggesting an important role of microRNAs in breast cancer development and progression. Certain microRNAs negatively regulate AIB1/ACTR, ERα, HER2 and HER3 and deregulation of these genes are well documented to modulate the resistance to tamoxifen in breast cancer. Therefore, we hypothesized that deregulated microRNAs might confer the aberrant expression of their target genes and the development of tamoxifen resistance in breast cancer. To identify microRNAs that might confer resistance to tamoxifen in breast cancer, we examined expression profiles of more than 600 microRNAs in a pair of tamoxifen-sensitive ZR75 and -resistant AK47 breast cancer cell lines using TaqMan Low Density Array (Applied Biosystems). Sixty-five microRNAs were identified substantially downmodulated in the tamoxifen-resistant cell line while 44 microRNAs were found to be upregulated. Consistent with others’ previous findings, our profiling results indicated that miR-221 and miR-222 were overexpressed in the tamoxifen-resistant breast cancer cells. Of the differentially expressed microRNAs, miR-449a and miR-449b were significantly downregulated in the resistant AK47 cells. miR-449a/b expression was also examined in 60 frozen breast tumors by TaqMan Individual MicroRNA Assay (Applied Biosystems). The expression of miR-449a/b was inversely correlated with tumor grade (miR-449a: OR=0.11, 95%CI=0.03-0.38, p<0.001; miR-449b: OR=0.23, 95%CI=0.07-0.70, p=0.008) and strongly associated with estrogen receptor status of the tumor (miR-449a: OR=5.57, 95%CI=1.67-18.55, p=0.003; miR-449b: OR=5.0, 95%CI=1.51-16.56, p=0.006). Our results suggest that miR-449a/b may influence tamoxifen sensitivity in breast cancer cells. Further functional studies are being performed to investigate the regulatory roles of the microRNAs in the development of tamoxifen resistance in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2040.

The Role of microRNAs in Development

The Role of microRNAs in Development

The Role of microRNAs in Development

The Role of microRNAs in Development

Accurate microRNA target prediction correlates with protein repression levels

BackgroundMicroRNAs are small endogenously expressed non-coding RNA molecules that regulate target gene expression through translation repression or messenger RNA degradation. MicroRNA regulation is performed through pairing of the microRNA to sites in the messenger RNA of protein coding genes. Since experimental identification of miRNA target genes poses difficulties, computational microRNA target prediction is one of the key means in deciphering the role of microRNAs in development and disease.ResultsDIANA-microT 3.0 is an algorithm for microRNA target prediction which is based on several parameters calculated individually for each microRNA and combines conserved and non-conserved microRNA recognition elements into a final prediction score, which correlates with protein production fold change. Specifically, for each predicted interaction the program reports a signal to noise ratio and a precision score which can be used as an indication of the false positive rate of the prediction.ConclusionRecently, several computational target prediction programs were benchmarked based on a set of microRNA target genes identified by the pSILAC method. In this assessment DIANA-microT 3.0 was found to achieve the highest precision among the most widely used microRNA target prediction programs reaching approximately 66%. The DIANA-microT 3.0 prediction results are available online in a user friendly web server at

Serum MicroRNAs Are Promising Novel Biomarkers

BackgroundCirculating nucleic acids (CNAs) offer unique opportunities for early diagnosis of clinical conditions. Here we show that microRNAs, a family of small non-coding regulatory RNAs involved in human development and pathology, are present in bodily fluids and represent new effective biomarkers.Methods and ResultsAfter developing protocols for extracting and quantifying microRNAs in serum and other body fluids, the serum microRNA profiles of several healthy individuals were determined and found to be similar, validating the robustness of our methods. To address the possibility that the abundance of specific microRNAs might change during physiological or pathological conditions, serum microRNA levels in pregnant and non pregnant women were compared. In sera from pregnant women, microRNAs associated with human placenta were significantly elevated and their levels correlated with pregnancy stage.Conclusions and SignificanceConsidering the central role of microRNAs in development and disease, our results highlight the medically relevant potential of determining microRNA levels in serum and other body fluids. Thus, microRNAs are a new class of CNAs that promise to serve as useful clinical biomarkers.

Victor Ambros

Victor Ambros