XRN2 promotes EMT and metastasis through regulating maturation of miR-10a

Zhang, H; Lü, Yan; Chen, E; Li, X; Lv, Ben; Vikis, Haris G.; Liu, P

doi:10.1038/onc.2017.39

Cited by 22 publications

(18 citation statements)

References 47 publications

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“…noted that XRN2 can perform a protective function by degrading aberrant pre‐RNA, and some studies have reported its function in mediating the maturation and decay of mammalian pre‐rRNAs, terminating premature transcription with the cooperation of other factors, and gene silencing at 3′ ends through interaction with other factors . One study reported that XRN2 can regulate the process of epithelial–mesenchymal transition and metastasis by modulating the maturation of miR‐10a, raising the possibility that XRN2 operates as a regulator in the hypothalamus to modulate activities of RNAs such as miRNAs related to reproduction, likely influencing gene expression and silencing, additionally, the degraded RNA fragments that cannot be eliminated by XRN2 on time may also influence gene expression or others. Overall, some DEPs, such as GH, HDAC4, and XRN2, whose abundances differed between PF and MF, may be responsible for, but may not those DEPs itself, different hormone release associated with the success of reproduction.…”

Section: Discussionmentioning

confidence: 99%

Identification of Prolificacy‐Related Differentially Expressed Proteins from Sheep (Ovis aries) Hypothalamus by Comparative Proteomics

Zhang

Tang

et al. 2019

Proteomics

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Reproduction, as a physiologically complex process, can significantly affect the development of the sheep industry. However, a lack of overall understanding to sheep fecundity has long blocked the progress in sheep breeding and husbandry. In the present study, the aim is to identify differentially expressed proteins (DEPs) from hypothalamus in sheep without FecB mutation in two comparison groups: polytocous (PF) versus monotocous (MF) sheep at follicular phase and polytocous (PL) versus monotocous (ML) sheep at luteal phase. Totally 5058 proteins are identified in sheep hypothalamus, where 22 in PF versus MF, and 39 proteins in PL versus ML are differentially expressed, respectively. A functional analysis is then conducted including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis to reveal the potential roles of these DEPs. The proteins ENSOARP00000020097, ENSOARP00000006714, growth hormone (GH), histone deacetylase 4 (HDAC4), and 5 -3 exoribonuclease 2 (XRN2) in PF versus MF, and bcl-2-associated athanogene 4 (BAG4), insulin-like growth factor-1 receptor (IGF1R), hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1), and transthyretin (TTR) in PL versus ML appear to modulate reproduction, presumably by influencing the activities of gonadotropin-releasing hormone (GnRH). This study provides an alternative method to identify DEPs associated with sheep prolificacy from the hypothalamus. The mass spectrometry data are available via ProteomeXchange with identifier PXD013822.

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Section: Discussionmentioning

confidence: 99%

Identification of Prolificacy‐Related Differentially Expressed Proteins from Sheep (Ovis aries) Hypothalamus by Comparative Proteomics

Zhang

Tang

et al. 2019

Proteomics

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“…A previous study reported that XRN2 binds pre-miR-10a in a DICER-independent manner and accelerates the maturation of miR-10a in human lung cancer cells 21 , but did not provide insights on the members of let-7 family. Here, we demonstrate that in a number of human cancer cell lines of lung, hepatic, and neuronal origin, XRN2 depletion led to the accumulation of a number of mature let-7 family members without any effect on their pri-or pre-miRNAs.…”

Section: Discussionmentioning

confidence: 92%

XRN2-mediated regulation of tumor suppressor microRNAs is of critical pathophysiological significance in Humans

Nalawade

Chowdhury

Chatterjee

2021

Preprint

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MicroRNAs (miRNAs) are critical regulators of diverse developmental and physiological processes in animals, and their dysregulation has been linked to various disorders and diseases. Not only multiple regulatory mechanisms acting at different levels of human miRNA biogenesis determine miRNA abundance and function, but a few recently identified factors by facilitating miRNA turnover also make critical contributions. We demonstrate that the ribonuclease XRN2, whose worm ortholog had previously been shown to actively degrade let-7 family of miRNAs, can degrade the mature forms of certain let-7 family members in multiple human cancer cell lines, without affecting their precursors. The XRN2-mediated turnover of let-7 has patho-physiological significance as XRN2 depletion results in a reduction in the expression of a number of oncogenes, and diminishes the proliferative and metastatic potential of cancer cells. The clinical relevance of these observations is also verified in tumour transcriptomics data from public RNA-sequencing datasets, where we observe that higher XRN2 mRNA expression is inversely correlated with the levels of mature let-7 miRNAs and associated with poor survival in hepatocellular carcinoma, lung adenocarcinoma, and glioblastoma. We also demonstrate that miRNA turnover is a step-wise process, where a miRNA is released from the grasp of Argonaute before its degradation. This yet unidentified miRNA releasing factor is proteinaceous in nature and its activity is kinetically linked with XRN2-mediated turnover of miRNAs. Our analyses of the patient-derived transcriptomics data also show that XRN2, via its regulation of let-7, affects pathways related to cellular proliferation, development, and signalling in a consistent manner across epithelial and glial cell lineages. Collectively, our studies suggest an important role of XRN2 in regulating cancer physiology through degradation of the let-7 family of miRNAs.

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“…Recently obtained data show that XRN1 negatively regulates autophagy in mammalian cells that thus reduces cell survival, which reinforces the evidence that this is a suppressor (Delorme-Axford et al, 2018). Contrary to this, 5′–3′ exonuclease XRN2 promotes EMT and metastasis through regulation of the processing of pre-miR-10a to mature miR-10a, and is a candidate inducer of spontaneous lung cancer (Zhang et al, 2017b; Figure 1C ).…”

Section: The Role Of Endogenous Mammalian Rnases In the Control Of Inmentioning

confidence: 98%

Surveillance of Tumour Development: The Relationship Between Tumour-Associated RNAs and Ribonucleases

Миронова

Vlassov

2019

Front. Pharmacol.

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Tumour progression is accompanied by rapid cell proliferation, loss of differentiation, the reprogramming of energy metabolism, loss of adhesion, escape of immune surveillance, induction of angiogenesis, and metastasis. Both coding and regulatory RNAs expressed by tumour cells and circulating in the blood are involved in all stages of tumour progression. Among the important tumour-associated RNAs are intracellular coding RNAs that determine the routes of metabolic pathways, cell cycle control, angiogenesis, adhesion, apoptosis and pathways responsible for transformation, and intracellular and extracellular non-coding RNAs involved in regulation of the expression of their proto-oncogenic and oncosuppressing mRNAs. Considering the diversity/variability of biological functions of RNAs, it becomes evident that extracellular RNAs represent important regulators of cell-to-cell communication and intracellular cascades that maintain cell proliferation and differentiation. In connection with the elucidation of such an important role for RNA, a surge in interest in RNA-degrading enzymes has increased. Natural ribonucleases (RNases) participate in various cellular processes including miRNA biogenesis, RNA decay and degradation that has determined their principal role in the sustention of RNA homeostasis in cells. Findings were obtained on the contribution of some endogenous ribonucleases in the maintenance of normal cell RNA homeostasis, which thus prevents cell transformation. These findings directed attention to exogenous ribonucleases as tools to compensate for the malfunction of endogenous ones. Recently a number of proteins with ribonuclease activity were discovered whose intracellular function remains unknown. Thus, the comprehensive investigation of physiological roles of RNases is still required. In this review we focused on the control mechanisms of cell transformation by endogenous ribonucleases, and the possibility of replacing malfunctioning enzymes with exogenous ones.

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XRN2 promotes EMT and metastasis through regulating maturation of miR-10a

Cited by 22 publications

References 47 publications

Identification of Prolificacy‐Related Differentially Expressed Proteins from Sheep (Ovis aries) Hypothalamus by Comparative Proteomics

Identification of Prolificacy‐Related Differentially Expressed Proteins from Sheep (Ovis aries) Hypothalamus by Comparative Proteomics

XRN2-mediated regulation of tumor suppressor microRNAs is of critical pathophysiological significance in Humans

Surveillance of Tumour Development: The Relationship Between Tumour-Associated RNAs and Ribonucleases

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