microRNA-1271 impedes the development of prostate cancer by downregulating PES1 and upregulating ERβ

J Transl Med. 2020 May 24;18(1):209. doi: 10.1186/s12967-020-02349-1.

Abstract

Background: As a nucleolar protein associated with ribosome biogenesis, pescadillo homolog 1 (PES1) has been reported to participate in the development of many cancers. However, its role in prostate cancer is not clearly defined. Therefore, the aim of this study is to explore the effects and the specific mechanism of PES1 in prostate cancer.

Methods: A microarray-based analysis was performed to analyze differentially expressed genes (DEGs) between prostate cancer and normal samples. Next, the interaction between PES1 and microRNA-1271 (miR-1271) was investigated using bioinformatics analysis in combination with dual-luciferase reporter gene assay. The expression of miR-1271 in prostate cancer cells and tissues was determined using RT-qPCR. Its effects on downstream estrogen receptor β (ERβ) signaling pathway were further examined. Moreover, we analyzed whether miR-1271 affects proliferation, apoptosis, migration and invasion of prostate cancer cells by EdU assay, flow cytometry, and Transwell assay. Lastly, a prostate cancer mouse model was conducted to measure their roles in the tumor growth.

Results: PES1 was identified as a prostate cancer-related DEG and found to be upregulated in prostate cancer. miR-1271, which was poorly expressed in both cells and tissues of prostate cancer, can specifically bind to PES1. Additionally, overexpression of miR-1271 activated the ERβ signaling pathway. Overexpression of miR-1271 or depletion of PES1 inhibited prostate cancer cell proliferation, migration and invasion, promoted apoptosis in vitro and suppressed tumor growth in vivo.

Conclusions: Taken together, overexpression of miR-1271 downregulates PES1 to activate the ERβ signaling pathway, leading to the delayed prostate cancer development. Our data highlights the potential of miR-1271 as a novel biomarker for the treatment of prostate cancer.

Keywords: Estrogen receptor β; Pescadillo homolog 1; Prostate cancer; microRNA-1271.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Estrogen Receptor beta* / genetics
  • Estrogen Receptor beta* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • MicroRNAs* / genetics
  • Prostatic Neoplasms* / genetics
  • RNA-Binding Proteins

Substances

  • Estrogen Receptor beta
  • MIRN1271 microRNA, human
  • MicroRNAs
  • PES1 protein, human
  • RNA-Binding Proteins