Nuclear microRNAs in normal hemopoiesis and cancer

Rasko, John E.J.; Wong, Justin

doi:10.1186/s13045-016-0375-x

Cited by 39 publications

(32 citation statements)

References 75 publications

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“…Mature KSHV miRNAs were found in both the cytoplasmic and nuclear fraction ( Fig 2A ). It is important to note that a cellular miRNA hsa-miR-16 is also distributed between the nucleus and the cytoplasm ( Fig 2A ), and such partial nuclear localization of mature miRNAs has been previously reported in other cell lines [ 26 , 27 ]. We probed the fractions for Ago-2 using western blotting ( Fig 2B ).…”

Section: Resultssupporting

confidence: 75%

microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus

et al. 2017

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Kaposi’s sarcoma (KS) is a highly prevalent cancer in AIDS patients, especially in sub-Saharan Africa. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of KS and other cancers like Primary Effusion Lymphoma (PEL). In KS and PEL, all tumors harbor latent KSHV episomes and express latency-associated viral proteins and microRNAs (miRNAs). The exact molecular mechanisms by which latent KSHV drives tumorigenesis are not completely understood. Recent developments have highlighted the importance of aberrant long non-coding RNA (lncRNA) expression in cancer. Deregulation of lncRNAs by miRNAs is a newly described phenomenon. We hypothesized that KSHV-encoded miRNAs deregulate human lncRNAs to drive tumorigenesis. We performed lncRNA expression profiling of endothelial cells infected with wt and miRNA-deleted KSHV and identified 126 lncRNAs as putative viral miRNA targets. Here we show that KSHV deregulates host lncRNAs in both a miRNA-dependent fashion by direct interaction and in a miRNA-independent fashion through latency-associated proteins. Several lncRNAs that were previously implicated in cancer, including MEG3, ANRIL and UCA1, are deregulated by KSHV. Our results also demonstrate that KSHV-mediated UCA1 deregulation contributes to increased proliferation and migration of endothelial cells.

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Section: Resultssupporting

confidence: 75%

microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus

et al. 2017

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“…Although intracellular trafficking of miRNA is of great importance for understanding its epigenetic gene silencing activity, the intracellular mobility and diffusion of miRNA remains a largely unexplored domain. However, it is undisputed that the gene regulatory function of miRNA is closely related to its sub‐cellular localization . AGO proteins and miRNA were found in different cellular compartments, including nucleus, endosomes, mitochondria, and lysosomes .…”

Section: Intracellular Translocation Of Mirna Toward Gjsmentioning

confidence: 99%

Potential mechanisms of microRNA mobility

Lemcke

Dávid

2018

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microRNAs (miRNAs) are important epigenetic modulators of gene expression that control cellular physiology as well as tissue homeostasis, and development. In addition to the temporal aspects of miRNA-mediated gene regulation, the intracellular localization of miRNA is crucial for its silencing activity. Recent studies indicated that miRNA is even translocated between cells via gap junctional cell-cell contacts, allowing spatiotemporal modulation of gene expression within multicellular systems. Although non coding RNA remains a focus of intense research, studies regarding the intra-and intercellular mobility of small RNAs are still largely missing. Emerging data from experimental and computational work suggest the involvement of transport mechanisms governing proper localization of miRNA in single cells and cellular syncytia. Based on these data, we discuss a model of miRNA translocation that could help to address the spatial aspects of miRNA function and the impact of miRNA molecules on the intercellular signaling network.

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“…Manipulation of miRNA expression in pain pathways from primary afferent nociceptors, DRG, spinal cord, and brain associated with pain perception prevents or reverses persistent inflammatory, neuropathic, and cancer pain behavior by post-transcription in cytoplasma (Park et al, 2014;Jiang et al, 2016;Gandla et al, 2017;Zhang et al, 2017). Growing findings suggest that the majority of miRNAs exist in both nucleus and cytoplasma, and some are preferentially enriched in the nucleus (Roberts, 2014;Rasko and Wong, 2017). Furthermore, the assembled Ago2-miRNA complexes are required for modulation of splicing or transcription of mRNA or circRNA through miRNA binding in nucleus.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-1224 Splicing CircularRNA-Filip1l in an Ago2-Dependent Manner Regulates Chronic Inflammatory Pain via Targeting Ubr5

Pan

Sun

et al. 2019

J. Neurosci.

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Dysfunctions of gene transcription and translation inthe nociceptive pathways play the critical role in development and maintenance of chronic pain. Circular RNAs (circRNAs) are emerging as new players in regulation of gene expression, but whether and how circRNAs are involved in chronic pain remain elusive. We showed here that complete Freund's adjuvant-induced chronic inflammation pain significantly increased circRNA-Filip1l (filamin A interacting protein 1-like) expression in spinal neurons of mice. Blockage of this increase attenuated complete Freund's adjuvant-induced nociceptive behaviors, and overexpression of spinal circRNA-Filip1l in naive mice mimicked the nociceptive behaviors as evidenced by decreased thermal and mechanical nociceptive threshold. Furthermore, we found that mature circRNA-Filip1l expression was negatively regulated by miRNA-1224 via binding and splicing of precursor of circRNA-Filip1l (pre-circRNA-Filip1l) in the Argonaute-2 (Ago2)-dependent manner. Increase of spinal circRNA-Filip1l expression resulted from the decrease of miRNA-1224 expression under chronic inflammation pain state. miRNA-1224 knockdown or Ago2 overexpression induced nociceptive behaviors in naive mice, which was prevented by the knockdown of spinal circRNA-Filip1l. Finally, we demonstrated that a ubiquitin protein ligase E3 component n-recognin 5 (Ubr5), validated as a target of circRNA-Filip1l, plays a pivotal role in regulation of nociception by spinal circRNA-Filip1l. These data suggest that miRNA-1224-mediated and Ago2-dependent modulation of spinal circRNA-Filip1l expression regulates nociception via targeting Ubr5, revealing a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain. Significance StatementcircRNAs are emerging as new players in regulation of gene expression. Here, we found that the increase of circRNA-Filip1l mediated by miRNA-1224 in an Ago2-dependent way in the spinal cord is involved in regulation of nociception via targeting Ubr5. Our study reveals a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain.

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Nuclear microRNAs in normal hemopoiesis and cancer

Cited by 39 publications

References 75 publications

microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus

microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus

Potential mechanisms of microRNA mobility

MicroRNA-1224 Splicing CircularRNA-Filip1l in an Ago2-Dependent Manner Regulates Chronic Inflammatory Pain via Targeting Ubr5

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