XRN2 promotes EMT and metastasis through regulating maturation of miR-10a.
MicroRNAs (miRNAs) have been proposed as critical regulatory molecules in the epithelial-mesenchymal transition (EMT) program. However, the roles of mature miRNA biogenesis during EMT process needs to be defined. Here we determined that increased expression of XRN2 induced EMT and promoted metastasis in vitro and in vivo. Furthermore, we uncovered that XRN2 functions as pro-metastatic gene, which accelerates miR-10a maturation by binding pre-miR-10a in a DICER-independent manner. These findings suggest that XRN2 is a novel regulator of EMT that contributes to the metastatic processes in lung cancer through a novel miRNA regulatory mechanism.
Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China.
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Zhang
Department of Gynecologic Oncology, The Affiliated Women's Hospital and Institute for Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
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Y
Lu
Division of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute for Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
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E
Chen
Division of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute for Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
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Li
Department of Gynecologic Oncology, The Affiliated Women's Hospital and Institute for Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
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Lv
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
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Vikis
Division of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute for Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China.|Department of Physiology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
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Liu
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005095:Exoribonucleases / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D011379:Prognosis; D016016:Proportional Hazards Models; D011485:Protein Binding; D012323:RNA Processing, Post-Transcriptional; D043244:Ribonuclease III / Q000378:metabolism
C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D005095:Exoribonucleases; C120903:XRN2 protein, human; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases