LSINCT5 activates Wnt/β-catenin signaling by interacting with NCYM to promote bladder cancer progression

Biochem Biophys Res Commun. 2018 Jul 20;502(3):299-306. doi: 10.1016/j.bbrc.2018.05.076. Epub 2018 May 30.

Abstract

Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are critically involved in tumor progression. In current study, we reported a novel lncRNA signature correlated with bladder cancer development. Particularly, the lncRNA long stress-induced noncoding transcript 5 (LSINCT5) is significantly upregulated in human bladder cancer cell lines and tumor specimens. Meanwhile, high LSINCT5 expression correlates with poor prognosis, enhances tumor sphere formation and invasion in vitro. In vivo xenograft tumor growth is also elevated by LSINCT5 overexpression. Mechanistic investigations showed that LSINCT5 could physically interact with NCYM, a de novo gene product from the MYCN cis-antisense RNA and inhibit GSK3β activity leading to enhanced Wnt/β-catenin signaling activation and epithelial mesenchymal transition (EMT). Taken together, our findings have created a novel LSINCT5 mediated process which facilitates bladder cancer progression and may provide a potential target for therapeutic intervention.

Keywords: Bladder cancer; EMT; LSINCT5; NCYM.

MeSH terms

  • Animals
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Knockdown Techniques
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • Up-Regulation
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology
  • Wnt Signaling Pathway
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • MYCNOS protein, human
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • beta Catenin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta