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Long noncoding RNA AK089579 inhibits epithelial-to-mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA-296-3p via DOK2 in peritoneal fibrosis.
FASEB J. 2019 04; 33(4):5112-5125.FJ

Abstract

Peritoneal fibrosis (PF) represents a well-recognized complication associated with continuous ambulatory peritoneal dialysis therapy, characterized by a reversible epithelial-to-mesenchymal transition (EMT) at the early stage. The aim of the current study was to investigate the effects linked with the long noncoding RNA (lncRNA) AK089579 on the EMT of peritoneal mesothelial cells (PMCs) as well as the associated regulatory mechanisms of AK089579 downstream of tyrosine kinase 2 (DOK2) and microRNA-296-3p (miR-296-3p). Enrichment analysis, gene intersection association analysis, and a gene-gene intersection network were initially constructed to ascertain whether AK089579 regulated the expression of DOK2 through the mediation of miR-296-3p via the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in PF. After the PF mouse model had been constructed, the expression of the proteins associated with the JAK2/STAT3 signaling pathway and EMT and PMC migration and invasion were all determined accordingly. Based on the obtained results, AK089579 was determined to function as a competing endogenous RNA for miR-296-3p while acting to up-regulate the expression of DOK2, which is a target gene of miR-296-3p. AK089579 was detected to confer an inhibitory effect on the activation of the JAK2/STAT3 signaling pathway, whereby the migration and invasion of PMCs among the mice models were suppressed. Meanwhile, up-regulated miR-296-3p and down-regulated DOK2 produced contrasting effects when compared with the aforementioned findings. Treatment with wp10066, a JAK2/STAS3 signaling pathway inhibitor, was shown to reverse the effects exerted by up-regulated miR-296-3p. Taken together, the central findings of the current study present evidence highlighting the capability of the lncRNA AK089579 to bind competitively to miR-296-3p and indirectly enhance the expression of DOK2, which in turn suppresses the activation of the JAK2/STAT3 signaling pathway, whereby the EMT, migration, and invasion of PMCs was inhibited in PF.-Zhang, X. W., Wang, L., Ding, H. Long noncoding RNA AK089579 inhibits epithelial-to-mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA-296-3p via DOK2 in peritoneal fibrosis.

Authors+Show Affiliations

Department of Pathology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China; and.Department of Nephrology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.Department of Nephrology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30652956

Citation

Zhang, Xiu Wei, et al. "Long Noncoding RNA AK089579 Inhibits Epithelial-to-mesenchymal Transition of Peritoneal Mesothelial Cells By Competitively Binding to microRNA-296-3p Via DOK2 in Peritoneal Fibrosis." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 33, no. 4, 2019, pp. 5112-5125.
Zhang XW, Wang L, Ding H. Long noncoding RNA AK089579 inhibits epithelial-to-mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA-296-3p via DOK2 in peritoneal fibrosis. FASEB J. 2019;33(4):5112-5125.
Zhang, X. W., Wang, L., & Ding, H. (2019). Long noncoding RNA AK089579 inhibits epithelial-to-mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA-296-3p via DOK2 in peritoneal fibrosis. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 33(4), 5112-5125. https://doi.org/10.1096/fj.201801111RR
Zhang XW, Wang L, Ding H. Long Noncoding RNA AK089579 Inhibits Epithelial-to-mesenchymal Transition of Peritoneal Mesothelial Cells By Competitively Binding to microRNA-296-3p Via DOK2 in Peritoneal Fibrosis. FASEB J. 2019;33(4):5112-5125. PubMed PMID: 30652956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long noncoding RNA AK089579 inhibits epithelial-to-mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA-296-3p via DOK2 in peritoneal fibrosis. AU - Zhang,Xiu Wei, AU - Wang,Lei, AU - Ding,Hong, Y1 - 2019/01/17/ PY - 2019/1/18/pubmed PY - 2020/1/14/medline PY - 2019/1/18/entrez KW - JAK2/STAT3 signaling pathway KW - ceRNA KW - peritoneal fibrosis SP - 5112 EP - 5125 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J VL - 33 IS - 4 N2 - Peritoneal fibrosis (PF) represents a well-recognized complication associated with continuous ambulatory peritoneal dialysis therapy, characterized by a reversible epithelial-to-mesenchymal transition (EMT) at the early stage. The aim of the current study was to investigate the effects linked with the long noncoding RNA (lncRNA) AK089579 on the EMT of peritoneal mesothelial cells (PMCs) as well as the associated regulatory mechanisms of AK089579 downstream of tyrosine kinase 2 (DOK2) and microRNA-296-3p (miR-296-3p). Enrichment analysis, gene intersection association analysis, and a gene-gene intersection network were initially constructed to ascertain whether AK089579 regulated the expression of DOK2 through the mediation of miR-296-3p via the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in PF. After the PF mouse model had been constructed, the expression of the proteins associated with the JAK2/STAT3 signaling pathway and EMT and PMC migration and invasion were all determined accordingly. Based on the obtained results, AK089579 was determined to function as a competing endogenous RNA for miR-296-3p while acting to up-regulate the expression of DOK2, which is a target gene of miR-296-3p. AK089579 was detected to confer an inhibitory effect on the activation of the JAK2/STAT3 signaling pathway, whereby the migration and invasion of PMCs among the mice models were suppressed. Meanwhile, up-regulated miR-296-3p and down-regulated DOK2 produced contrasting effects when compared with the aforementioned findings. Treatment with wp10066, a JAK2/STAS3 signaling pathway inhibitor, was shown to reverse the effects exerted by up-regulated miR-296-3p. Taken together, the central findings of the current study present evidence highlighting the capability of the lncRNA AK089579 to bind competitively to miR-296-3p and indirectly enhance the expression of DOK2, which in turn suppresses the activation of the JAK2/STAT3 signaling pathway, whereby the EMT, migration, and invasion of PMCs was inhibited in PF.-Zhang, X. W., Wang, L., Ding, H. Long noncoding RNA AK089579 inhibits epithelial-to-mesenchymal transition of peritoneal mesothelial cells by competitively binding to microRNA-296-3p via DOK2 in peritoneal fibrosis. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/30652956/Long_noncoding_RNA_AK089579_inhibits_epithelial_to_mesenchymal_transition_of_peritoneal_mesothelial_cells_by_competitively_binding_to_microRNA_296_3p_via_DOK2_in_peritoneal_fibrosis_ L2 - https://doi.org/10.1096/fj.201801111RR DB - PRIME DP - Unbound Medicine ER -