Long Non-Coding RNA PCAT19 Regulates the Malignant Progression of Bladder Cancer through the miR-335-5p/IER2 Axis

Crit Rev Eukaryot Gene Expr. 2022;32(8):81-94. doi: 10.1615/CritRevEukaryotGeneExpr.2022043175.

Abstract

Bladder cancer is a common urological tumor, and its development process is complicated. Many long non-coding RNAs (lncRNAs), including PCAT19, have a regulatory role in cell development and gene expression, and is widely involved in the occurrence and development of a variety of cancers. We studied the changes in cell function through MTT assay, flow cytometer, transwell assay, etc. Several molecular assays are employed to explore these molecular mechanistic aspects, such as luciferase reporter, reverse transcription quantitative polymerase chain reaction, and Western blot. In addition, we also constructed a mouse bladder cancer xenograft model to verify the function of the PCAT19/miR-335-5p/IER2 signal axis in vivo. PCAT19 is upregulated in bladder cancer tissues, while miR-335-5p is downregulated, and the expression of PCAT19 and miR-335-5p is negatively correlated. The survival rate of bladder cancer patients in the PCAT19 upregulated group or miR-335-5p downregulated group was lower. After overexpression of PCAT19, the amount of miR-335-5p in cell is decreased, and the IER2 expression is increased. It can significantly promote the vitality, proliferation, migration and invasion capabilities of bladder cancer cells, and significantly inhibit cell apoptosis. Studies on molecular mechanisms show that PCAT19 can regulate the miR-335-5p/IER2 signal axis both in vivo and in vitro. PCAT19, which is upregulated in bladder cancer tissue, interacts with miR-335-5p to regulate the expression of downstream target gene IER2, forming a complete PCAT19/miR-335-5p/IER2 signal regulation axis, and ultimately affect the malignant progression of bladder cancer both in vivo and in vitro.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immediate-Early Proteins* / genetics
  • Immediate-Early Proteins* / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • Urinary Bladder Neoplasms* / genetics
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Immediate-Early Proteins
  • MIRN335 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Ier2 protein, mouse