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Upregulation of lncRNA DGCR5 correlates with better prognosis and inhibits bladder cancer progression via transcriptionally facilitating P21 expression.

Abstract
Mounting studies show that long noncoding RNAs (lncRNAs) could affect human cancer progression, including bladder cancer (BCa). LncRNA DiGeorge syndrome critical region gene 5 (DGCR5) has been proven to be involved in lung cancer, pancreatic ductal adenocarcinoma, and hepatocellular carcinoma. However, the function of DGCR5 in BCa remains largely unknown. Here, we found that DGCR5 expression was significantly downregulated in BCa tissues compared with adjacent normal tissues. Higher expression of DGCR5 predicted higher survival rate in BCa patients. Functional experiments indicated that DGCR5 overexpression markedly inhibited that proliferation, colony formation, and cell-cycle progression in BCa cells. Furthermore, ectopic expression of DGCR5 led to decreased BCa cell migration, invasion, and epithelial-mesenchymal transition while promoting apoptosis. In vivo xenograft assay also illustrated that DGCR5 overexpression inhibited BCa growth. In the mechanism, we found that DGCR5 interacted with AT-rich interaction domain 1A (ARID1A), a chromatin remodeling protein, to promote P21 transcription. Knockdown of P21 could significantly rescue the suppressed proliferation, migration, and invasion of BCa cells by DGCR5 overexpression. In summary, our study demonstrated that DGCR5 transcriptionally promotes P21 expression to suppress BCa progression.
AuthorsChen Fang, Wei He, Tianyuan Xu, Jun Dai, Le Xu, Fukang Sun
JournalJournal of cellular physiology (J Cell Physiol) Vol. 234 Issue 5 Pg. 6254-6262 (05 2019) ISSN: 1097-4652 [Electronic] United States
PMID30238982 (Publication Type: Journal Article)
Copyright© 2018 Wiley Periodicals, Inc.
Chemical References
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Long Noncoding
  • long noncoding RNA DGCR5, human
Topics
  • Animals
  • Cyclin-Dependent Kinase Inhibitor p21 (biosynthesis, genetics)
  • Disease Progression
  • Gene Expression Regulation, Neoplastic (genetics)
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • Prognosis
  • RNA, Long Noncoding (genetics)
  • Up-Regulation
  • Urinary Bladder Neoplasms (genetics, metabolism, pathology)

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