Long non-coding RNA HULC promotes bladder cancer cells proliferation but inhibits apoptosis via regulation of ZIC2 and PI3K/AKT signaling pathway

Cancer Biomark. 2017 Dec 6;20(4):425-434. doi: 10.3233/CBM-170188.

Abstract

Background: Bladder cancer is the fourth most common malignancy among men urinary system and it is a complex disease caused by genetic and environmental factors.

Objective: This study aimed to evaluate the effects of hepatocellular carcinoma up-regulated long non-coding RNA (lncRNA HULC) on bladder cancer and to reveal the potential mechanisms.

Methods: The expression level of HULC in 276 bladder cancer patients was detected. The association of HULC level with patient recurrence was performed by Kaplan-Meier and log-rank test. Moreover, T24 and RT4 cells were transfected with HULC and ZIC2 targeted siRNAs, HULC expressing vector and corresponding controls. Subsequently, cell viability, apoptosis and tumorigenesis were examined.

Results: The expression level of HULC was increased in bladder cancer tissues. High expression of HULC was correlated with advanced clinical stage and lower recurrence-free rate. HULC was remarkably promoted cell viability but inhibited apoptosis, meanwhile conspicuously increased the expression of Cyclin A/D1/E and Bcl-2. Xenograft tumor model showed that HULC promoted tumor weights in vivo.

Conclusions: LncRNA HULC promoted bladder cancer cells proliferation and inhibited apoptosis.

Keywords: Bladder cancer; PI3K/AKT; ZIC2; cell apoptosis; cell proliferation; lncRNA HULC.

Publication types

  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Heterografts
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Nuclear Proteins / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Long Noncoding / genetics*
  • Recurrence
  • Signal Transduction
  • Transcription Factors / genetics*
  • Tumor Burden
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology

Substances

  • HULC long non-coding RNA, human
  • Nuclear Proteins
  • RNA, Long Noncoding
  • Transcription Factors
  • ZIC2 protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt