Role Of miRNAs In Development Research Articles

Abstract 2024: Over-expression of miR-106b in metastatic hepatocellular carcinoma using an orthotopic metastasis animal model

Abstract Hepatocellular carcinoma (HCC) is one the most fatal cancers worldwide. Early diagnosis is crucial for curing the disease. However, patients are often diagnosis at late-stage with distant metastasis, and the prognosis of metastatic HCC is poor. Molecular pathological studies confirm that gene expression alteration plays a critical role in disease progression. Recently it has been discovered that microRNA (miRNA) can alter the gene expression at post-transcription level. This study aimed to elucidate the role of miRNA in development of metastatic HCC using an orthotopic animal model and the molecular pathway involved. Orthotopic metastasis animal model was established by implanting HCC cell lines onto the liver of the SCID mice. Tumor growth was monitored by in vivo imaging system. Primary tumor and lung metastasis were observed after 12 weeks of inoculation. Tumor were then excised and established into primary tumor cell lines (PT) and lung metastatic cell lines (LM). Functional studies comparing the PT and LM cell lines derived from HCC cell line PLC demonstrated higher cell invasion and migration ability in the metastatic cell line compared with the primary tumor cell line. In addition, the LM cell line possessed more stress fiber than the PT cell line. The PLC-derived cell lines and another metastatic HCC cell line, MHCC97H-derived cell lines were subjected to the miRNA microarray analysis. Fifteen human miRNAs were found to be differentially expressed in the LM cell lines when compared to the PT cell lines. miR-106b was one of the miRNAs which was over-expressed in LM cell lines. We further confirmed our findings in HCC clinical sample and found that miR-106b was over-expressed in HCC tumor compared with the adjacent non-tumor tissue, and its expression was significantly associated with the tumor grade (p=0.018). MicroRNA knock-down study was performed by using the miR-106b LNA knock-down probe. The miR-106b knock-down reverted the cell migration phenotype, and fluorescent staining of stress fiber formation showed that the miR-106b knock-down cells have less stress fiber formation than the parental cell lines and the scramble control. We further studied the expression of E-cadherin in PLC-PT, PLC-LM, the scramble control and the miR-106b knock-down cell lines. Our result demonstrated that miR-106b expression inversely correlated with E-cadherin level. Since decrease of E-cadherin expression is the hallmark for epithelia-mesenchymal transition (EMT), further studies will focus on the role of miR-106b in EMT of HCC cells. 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 2024.

MicroRNAs Potentiate Neural Development

MicroRNAs (miRNAs) are endogenously expressed noncoding RNAs that regulate mRNA expression. In vertebrates, more distinct miRNAs are expressed in the brain than in any other tissue, where they are hypothesized to function in neural development. Recent reports describing the effects of specific miRNAs during development, and studies employing miRNA depletion as neural commitment proceeds in the embryo, support a requisite role for miRNAs in cell-fate decisions and provide clues to their function in other aspects of nervous system development.

Lost in translation: an assessment and perspective for computational microRNA target identification

MicroRNAs (miRNAs) are a class of short endogenously expressed RNA molecules that regulate gene expression by binding directly to the messenger RNA of protein coding genes. They have been found to confer a novel layer of genetic regulation in a wide range of biological processes. Computational miRNA target prediction remains one of the key means used to decipher the role of miRNAs in development and disease. Here we introduce the basic idea behind the experimental identification of miRNA targets and present some of the most widely used computational miRNA target identification programs. The review includes an assessment of the prediction quality of these programs and their combinations. Supplementary data are available at Bioinformatics online.

DIANA-microT web server: elucidating microRNA functions through target prediction

Computational microRNA (miRNA) target prediction is one of the key means for deciphering the role of miRNAs in development and disease. Here, we present the DIANA-microT web server as the user interface to the DIANA-microT 3.0 miRNA target prediction algorithm. The web server provides extensive information for predicted miRNA:target gene interactions with a user-friendly interface, providing extensive connectivity to online biological resources. Target gene and miRNA functions may be elucidated through automated bibliographic searches and functional information is accessible through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The web server offers links to nomenclature, sequence and protein databases, and users are facilitated by being able to search for targeted genes using different nomenclatures or functional features, such as the genes possible involvement in biological pathways. The target prediction algorithm supports parameters calculated individually for each miRNA:target gene interaction and provides a signal-to-noise ratio and a precision score that helps in the evaluation of the significance of the predicted results. Using a set of miRNA targets recently identified through the pSILAC method, the performance of several computational target prediction programs was assessed. DIANA-microT 3.0 achieved there with 66% the highest ratio of correctly predicted targets over all predicted targets. The DIANA-microT web server is freely available at www.microrna.gr/microT.

Use of miRNA expression profiling to identify novel biomarkers.

Micro (mi)RNAs are small, noncoding RNAs that regulate gene expression through binding to the 3´-untranslated region of mRNAs by complementary base pairing and mainly act through cleavage or translational inhibition of mRNAs. Recent studies have shown the roles of miRNAs in development and cancer, revealing the physiological and pathological importance of these tiny molecules. Therefore, as with mRNAs, researchers have focused on the global analyses of miRNAs to seek their potential use as biomarkers for physiological and pathological states of a cell. Methods developed for miRNA profiling are briefly discussed in this review. Recent evidences supporting the use of miRNAs as biomarkers in both differentiation and cancer are presented. The profiling studies may highlight the clinical relevance of miRNAs and will enable the researchers to uncover the enormous potential of these tiny molecules. In the near future, selected miRNA genes based on expression abnormalities will be tested as candidates for miRNA-based cancer gene therapy.

MicroRNAs under the microscope

Once regarded as a biological anomaly, microRNAs (miRNAs) have since been recognized as a prevalent RNA species that regulates a wide array of biological processes, from fat storage and insulin secretion, to apoptosis and cell growth. Recent studies show that miRNAs are expressed at precise times and locations in embryonic development. Moreover, disruption of miRNA processing triggers widespread developmental defects. These findings bolster the idea that miRNAs also regulate multiple aspects of embryonic development. This primer focuses on the emerging roles of miRNAs in development. The basics of miRNA biogenesis and miRNA and mRNA target identification are covered, with an emphasis on miRNA function in development. The primer also features a dialog about current topics in the field.