Targeting of AKT1 by miR-143-3p Suppresses Epithelial-to-Mesenchymal Transition in Prostate Cancer

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Abstract

An altered expression of miR-143-3p has been previously reported in prostate cancer where it is purported to play a tumor suppressor role. Evidence from other cancers suggests miR-143-3p acts as an inhibitor of epithelial-to-mesenchymal transition (EMT), a key biological process required for metastasis. However, in prostate cancer the interaction between miR-143-3p and EMT-associated mechanisms remains unclear. Therefore, this paper investigated the link between miR-143-3p and EMT in prostate cancer using in vitro and in silico analyses. PCR detected that miR-143-3p expression was significantly decreased in prostate cancer cell lines compared to normal prostate cells. Bioinformatic analysis of The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) data showed a significant downregulation of miR-143-3p in prostate cancer, correlating with pathological markers of advanced disease. Functional enrichment analysis confirmed the significant association of miR-143-3p and its target genes with EMT. The EMT-linked gene AKT1 was subsequently shown to be a novel target of miR-143-3p in prostate cancer cells. The in vitro manipulation of miR-143-3p levels significantly altered the cell proliferation, clonogenicity, migration and expression of EMT-associated markers. Further TCGA PRAD analysis suggested miR-143-3p tumor expression may be a useful predictor of disease recurrence. In summary, this is the first study to report that miR-143-3p overexpression in prostate cancer may inhibit EMT by targeting AKT1. The findings suggest miR-143-3p could be a useful diagnostic and prognostic biomarker for prostate cancer.
Original languageEnglish
Article number2207
Pages (from-to)1-18
Number of pages18
JournalCells
Volume12
Issue number18
Early online date5 Sept 2023
DOIs
Publication statusPublished online - 5 Sept 2023

Bibliographical note

Funding Information:
This research was funded by the Department for the Economy (DfE), Northern Ireland, as a PhD studentship (DFE2021) secured by D.J.M. and C.E.W. and awarded to L.A.

Publisher Copyright:
© 2023 by the authors.

Keywords

  • prostrate cancer
  • microRNA
  • miR-143p
  • epithelial-to-mesenchymal transition
  • AKT1
  • biomarker
  • miR-143-3p
  • prostate cancer

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