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Tumour-suppressive miRNA-26a-5p and miR-26b-5p inhibit cell aggressiveness by regulating PLOD2 in bladder cancer

K Miyamoto1, N Seki2, R Matsushita1

  • 1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.

British Journal of Cancer
|June 17, 2016
PubMed
Abstract

Insights

MicroRNAs miR-26a-5p and miR-26b-5p are downregulated in bladder cancer (BC). Their restoration inhibits BC cell invasion, and PLOD2 is identified as a direct target, serving as a prognostic marker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) miR-26a-5p and miR-26b-5p are recognized as tumor suppressors in multiple cancers.
  • Their specific roles and regulatory targets in bladder cancer (BC) remain to be fully elucidated.

Purpose of the Study:

  • To investigate the functional significance of miR-26a-5p and miR-26b-5p in bladder cancer.
  • To identify the direct molecular targets regulated by these miRNAs in BC.

Main Methods:

  • Functional assays were conducted in bladder cancer cell lines following miRNA transfection.
  • In silico analysis and luciferase reporter assays were employed to identify miRNA target genes.
  • Kaplan-Meier analysis was used to assess the association between gene expression and overall survival (OS) in BC patients.

Main Results:

  • miR-26a-5p and miR-26b-5p expression was significantly reduced in bladder cancer tissues.
  • Reintroduction of these miRNAs suppressed bladder cancer cell migration and invasion.
  • Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was identified as a direct target gene.
  • High PLOD2 expression correlated with significantly shorter overall survival in bladder cancer patients (P=0.0153).

Conclusions:

  • PLOD2, an enzyme involved in extracellular matrix stiffness, is directly regulated by miR-26a-5p and miR-26b-5p.
  • PLOD2 may serve as a valuable prognostic biomarker for bladder cancer patients.

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