Tetracycline-inducible shRNA targeting long non-coding RNA PVT1 inhibits cell growth and induces apoptosis in bladder cancer cells

Oncotarget. 2015 Dec 1;6(38):41194-203. doi: 10.18632/oncotarget.5880.

Abstract

Recent studies show that long non-coding RNAs (lncRNAs) may be significant functional regulators in tumor development, including bladder cancer. Here, we found that PVT1 was upregulated in bladder cancer tissues and cells. Further experiments revealed that PVT1 promoted cell proliferation and suppressed cell apoptosis. Furthermore we also used the emerging technology, synthetic biology, to create tetracycline-inducible small hairpin RNA (shRNA) vectors which silenced PVT1 in a dosage-dependent manner to inhibit the progression of bladder cancer. In conclusion, data suggest that PVT1 could be an oncogene and may be a therapeutic target in bladder cancer. Synthetic "tetracycline-on" switch system can be used to quantitatively control the expression of PVT1 in bladder cancer in response to different concentration of doxycycline to suppress the progression of bladder cancer.

Keywords: PVT1; bladder cancer; lncRNAs; synthetic biology; tetracycline-inducible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetracycline / pharmacology
  • Up-Regulation
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology

Substances

  • PVT1 long-non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Tetracycline