miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• MicroRNAs miR-148-3p and miR-152-3p are recognized tumor suppressors in various cancers.
• Their specific role and synergistic effect in prostate cancer (PCa) require further elucidation.

Purpose of the Study:

• To investigate the synergistic function of miR-148-3p and miR-152-3p in prostate cancer.
• To determine the molecular mechanism underlying their tumor-suppressive activity in PCa.

Main Methods:

• Bioinformatics and luciferase reporter assays to confirm binding of miR-148-3p/152-3p to KLF4 3'-UTR.
• In vitro and in vivo studies using PCa cell lines and mouse xenograft models to assess tumor growth inhibition.
• Analysis of miR-148-3p, miR-152-3p, and KLF4 expression in PCa tissues.

Main Results:

• miR-148-3p and miR-152-3p expression were significantly reduced in PCa tissues, while KLF4 protein expression was elevated.
• KLF4 3'-UTR contains conserved binding sites for miR-148-3p and miR-152-3p.
• miR-148-3p/152-3p mimics inhibited PCa cell growth in vitro and in vivo, whereas inhibitors increased KLF4 and cell growth. KLF4 overexpression counteracted the tumor-suppressive effects.

Conclusions:

• The miR-148-3p/152-3p family functions as a tumor suppressor in prostate cancer.
• This tumor-suppressive role is mediated through the direct repression of Kruppel-like factor 4 (KLF4) expression.