MicroRNA-3619-5p suppresses bladder carcinoma progression by directly targeting β-catenin and CDK2 and activating p21

Cell Death Dis. 2018 Sep 20;9(10):960. doi: 10.1038/s41419-018-0986-y.

Abstract

Current studies indicate that microRNAs (miRNAs) are widely decreased in various tumors and function as tumor suppressors by inhibiting cancer cell proliferation, survival, invasion, and migration. The potential application of using miRNAs to predict therapeutic responses to multiple types of cancer treatment holds high promise. In current study, we demonstrate that miR-3619-5p is downregulated in bladder cancer (BCa) tissues and cells. Exogenous overexpression of miR-3619-5p in BCa cells inhibits proliferation, migration, and invasion. Moreover, a nude mouse xenograft model shows that miR-3619-5p inhibits BCa cell growth. We also demonstrate that miR-3619-5p leads to the activation of p21 by targeting its promoter in BCa cells. Enforced miR-3619-5p expression consistently leads to the downregulation of β-catenin and cyclin-dependent kinase 2 (CDK2) through predicted binding sites within the β-catenin and CDK2 3'-untranslated regions (UTRs), respectively. Moreover, β-catenin and CDK2 knockdown is able to mimic BCa cells growth and metastasis effects induced by overexpressing miR-3619-5p. We further confirm that miR-3619-5p inhibits Wnt-β-catenin signal pathway and EMT progression in BCa cells. We also found that miR-3619-5p-induced growth arrest and metastasis inhibition are p21-dependent in BCa cells. Taken together, these results confirm that miR-3619-5p plays a tumor suppressive role in BCa by interfering with cell growth and metastasis and may serve as a potential therapeutic target in BCa treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Urinary Bladder / metabolism*
  • Urinary Bladder / pathology*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology*
  • Wnt Signaling Pathway / genetics
  • Wnt Signaling Pathway / physiology
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • MIRN-3619 microRNA, human
  • MicroRNAs
  • beta Catenin
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2