The big world of small RNAs

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Science (Impact Factor: 33.61). 10/2005; 309(5740):1519-24. DOI: 10.1126/science.1111444
Source: PubMed


Small RNA guides—microRNAs, small interfering RNAs, and repeat-associated small interfering RNAs, 21 to 30 nucleotides in
length—shape diverse cellular pathways, from chromosome architecture to stem cell maintenance. Fifteen years after the discovery
of RNA silencing, we are only just beginning to understand the depth and complexity of how these RNAs regulate gene expression
and to consider their role in shaping the evolutionary history of higher eukaryotes.

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    • "MiRNAs are a class of noncoding RNA duplex molecules that are approximately 21–23 nucleotides in length, which regulate the stability or the translational efficiency of target mRNAs (Zamore and Haley, 2005). MiRNAs are formed through primary transcription in the nucleus by means of RNA polymerase , also referred to as long primary transcripts (pre-miRNAs), processed into 70-to 100-nucleotide sequences by RNAse III Drosha, and then exported into the cytoplasm where they are further processed to generate mature miRNA species of the form of double stranded RNAs (Vasudevan et al., 2007). "
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    • "Let-7a was found to regulate the drug-induced apoptosis in cells by targeting caspase-3 [127]. Many studies reported that let-7a may serve as tumor suppressor miRNAs because of its downregulation in association with the overexpression of oncogenes as RAS and HMGA2 [127] [128]. Besides, let-7 also modulates cell proliferation [129]. "
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    ABSTRACT: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. MicroRNAs (miRNAs) are naturally-occurring, non-coding small RNA molecules that can modulate protein coding-genes, which makes it contributing to nearly all the physiological and pathological processes. Progression of breast cancer and resistance to endocrine therapies has been attributed to the possibility of hormone-responsive miRNAs involved in the regulation of certain signaling pathways. Methodology This review introduces better understanding of miRNAs to provide promising advances for treatment. miRNAs have multiple targets, and they were found to regulate different signaling pathways; consequently it is important to characterize their mechanisms of action and their cellular targets in order to introduce miRNAs as novel and promising therapies. This review summarizes the molecular mechanisms of miRNAs in TGF-Beta signaling, apoptosis, metastasis, cell cycle, ER-signaling, and drug resistance. Finally, miRNAs will be introduced as promising molecules to be used in the fight against breast cancer and its developed drug resistance. Copyright © 2014. Published by Elsevier Inc.
    Clinical Biochemistry 12/2014; 48(6). DOI:10.1016/j.clinbiochem.2014.12.013 · 2.28 Impact Factor
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    • "MicroRNAs (miRNAs), which encode small non-coding RNAs of approximately 22 nucleotides, are now recognized as a very large gene family. Mature miRNAs are thought to regulate the negative expression of a large number of genes carrying target sites within 3′ untranslated regions (UTR) [2]. Recent studies demonstrate that miRNAs may act as activators of tumor metastasis by acting on multiple signaling pathways involved in metastasis [3,4]. "
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    ABSTRACT: Background Recently, miR-10b is identified as a miRNA highly expressed in many human cancers, promoting cell migration and invasion. However, the specific function of miR-10b in hepatocellular carcinoma (HCC) is unclear at this point.Methods The miR-10b expression levels in 60 paired different TNM Stage HCC tumor tissues compared with adjacent non-tumor (ANT) tissues, normal tissue control (8 benign tumor and 7 normal liver tissues), 3 normal liver and 7 HCC cell lines were measured by real-time quantitative RT-PCR and to evaluate their association with HCC clinicopathologic features. Invasion assay, MTT proliferation assay and wound-healing assay were performed to test the invasion and proliferation of HCC cell after transfection. The effect of miR-10b on HCC in vivo was validated by murine xenograft model.ResultsWe found that miR-10b expression was increased in human HCC tissues and cell lines compared with normal control, respectively. The expression of miR-10b was correlated with HCC metastatic ability. Overexpression of miR-10b in MHCC-97 L cells increased cell motility and invasiveness, whereas inhibition of miR-10b in MHCC-97H cells reduced cell motility and invasiveness in vitro and in vivo. We also showed that HOXD10 was negatively regulated by miR-10b at the posttranscriptional level, via a specific target site within the 3¿UTR by luciferase reporter assay. Furthermore, we found that miR-10b induced HCC cell invasion and migration by modulating the HOXD10 target gene RhoC, uPAR, MMP-2 and MMP-9 expression.Conclusions Our results suggested that miR-10b was overexpressed in HCC and promoted HCC cell migration and invasion through the HOXD10/ RhoC/ uPAR/ MMPs pathway which may provide a novel bio-target for HCC therapy.
    Journal of Translational Medicine 09/2014; 12(1):234. DOI:10.1186/s12967-014-0234-x · 3.93 Impact Factor
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