MiRNA-145-5p expression and prospective molecular mechanisms in the metastasis of prostate cancer

Zhi-Guang Huang1, Yu Sun2, Gang Chen1

  • 1Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China.

IET Systems Biology
|February 2, 2021
PubMed

Insights

MicroRNA-145-5p is downregulated in metastatic prostate cancer (PCa), suggesting it may inhibit metastasis by targeting TOP2A. This microRNA could serve as a biomarker for detecting metastatic PCa.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biomarker Discovery

Background:

  • The role of microRNA-145-5p in prostate cancer (PCa) metastasis is not well understood.
  • Identifying molecular mechanisms driving PCa metastasis is crucial for improved diagnostics and therapeutics.

Purpose of the Study:

  • To investigate the clinicopathological significance and molecular mechanisms of miRNA-145-5p in prostate cancer metastasis.
  • To identify potential molecular targets of miRNA-145-5p involved in PCa progression.

Main Methods:

  • Analysis of miRNA expression datasets (miRNA-chip, miRNA-sequencing) from localized and metastatic PCa cohorts.
  • Bioinformatic analysis including target prediction, protein-protein interaction (PPI) network analysis.
  • Validation of target gene expression using Gene-chip, RNA-sequencing, and immunohistochemistry (IHC) on clinical PCa samples.

Main Results:

  • miRNA-145-5p expression was significantly reduced in metastatic PCa compared to localized PCa (SMD = -1.26, AUC = 0.86).
  • TOP2A was identified as a key target gene, showing an inverse correlation with miRNA-145-5p expression in both metastatic (r = -0.504) and primary PCa (r = -0.281).
  • TOP2A mRNA and protein were consistently upregulated in PCa versus non-PCa tissues, and significantly higher in metastatic than localized PCa (SMD = 1.72, AUC = 0.91).

Conclusions:

  • miRNA-145-5p may play a role in inhibiting prostate cancer metastasis by targeting TOP2A.
  • The miRNA-145-5p/TOP2A axis presents a potential biomarker for the detection of metastatic prostate cancer.

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