LncROR Promotes Bladder Cancer Cell Proliferation, Migration, and Epithelial-Mesenchymal Transition

Cell Physiol Biochem. 2017;41(6):2399-2410. doi: 10.1159/000475910. Epub 2017 May 3.

Abstract

Background: LncRNA ROR, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, the molecular biological function in bladder cancer has not been clearly elucidated. The aim of this study is to explore ROR expression levels and evaluated its function in bladder cancer.

Methods: LncRNA ROR expression levels in the 36 pairs of bladder cancer tissues (and corresponding non-tumor tissues) and bladder cancer cells were assessed by qRT-PCR. MTT assay, colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays, attachment/detachment and western blotting were performed to assess the effects of ROR on proliferation, apoptosis, migration/invasion and epithelial-to-mesenchymal (EMT) phenotypes in BC cells in vitro. ZEB1 is target of ROR. Rescue assays were performed to further confirm that ROR contributes to the progression of BC cells through targeting ZEB1.

Results: LncRNA ROR was up-regulated in bladder cancer tissues (compared to adjacent non-tumor tissues) and was almost overexpression in bladder cancer cells (compared with normal urothelial cell line SVHUC-1 cells). Increased lncRNA ROR expression significantly promoted tumor cells proliferation, inhibited cells apoptosis, facilitated cells metastasis and contributed to the formation of EMT phenotype. While down-regulated ROR could obviously inhibit cells proliferation, promote cells apoptosis, inhibit metastasis and reverse EMT to MET. ZEB1 was a target gene of ROR and was positive correlation with the level of ROR in cancer tissues.

Conclusion: These results indicated that lncRNA ROR was associated with tumor progression in bladder cancer cells.

Keywords: Bladder cancer; EMT; Migration; Proliferation; lncRNA ROR.

MeSH terms

  • Aged
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Up-Regulation
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / physiopathology*
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism
  • beta Catenin / metabolism

Substances

  • Cadherins
  • Linc-RNA-RoR, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • beta Catenin