# Transcriptomic Insights into lncRNA–miRNA–mRNA Networks Regulating Angiogenesis and Metastasis in Prostate Cancer

## TL;DR

This study explores how non-coding RNAs regulate blood vessel growth and cancer spread in prostate cancer, identifying a key RNA network that could be used as a biomarker or treatment target.

## Contribution

The study identifies a novel lncRNA–miRNA–mRNA axis (LINC00261–miR-206–HIF1A) involved in prostate cancer angiogenesis and metastasis.

## Key findings

- miRNAs like hsa-miR-183-5p and hsa-miR-216a-5p are upregulated in metastatic prostate cancer and linked to pro-angiogenic signaling.
- The LINC00261–miR-206–HIF1A axis is a central regulatory module in PCa progression, validated through RT-qPCR in patient samples.
- Downregulation of LINC00261 and miR-206, along with HIF1A overexpression, is significantly associated with metastatic disease.

## Abstract

Prostate cancer (PCa) is a leading cause of cancer-related mortality in men and is often characterized by aggressive growth and bone metastasis. Angiogenesis plays a central role in tumor progression and dissemination. This study aimed to explore the regulatory roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in angiogenesis and metastasis during PCa progression. Publicly available RNA-seq datasets were analyzed to identify differentially expressed miRNAs between metastatic (N1) and nonmetastatic (N0) PCa. Bioinformatic tools were used to reconstruct co-regulatory networks involving miRNAs, lncRNAs, and angiogenesis-related mRNAs. RT-qPCR was performed on serum-derived liquid biopsies from N0 and N1 patients and healthy controls to validate the key regulatory axes. Transcriptomic analysis revealed that miRNAs such as hsa-miR-183-5p and hsa-miR-216a-5p were upregulated in N1 PCa and associated with pro-angiogenic signaling, whereas hsa-miR-206 and hsa-miR-184, known for their anti-angiogenic functions, were downregulated. Network analysis identified the LINC00261–miR-206–HIF1A axis as the central regulatory module. RT-qPCR validation confirmed the significant downregulation of LINC00261 and miR-206, along with HIF1A overexpression in N1 samples compared to N0 and controls (p < 0.001), supporting in silico predictions. These findings highlight the role of ncRNA-mediated regulation of PCa angiogenesis and metastasis. The LINC00261–miR-206–HIF1A axis may serve as a promising noninvasive biomarker and potential therapeutic target. The integration of computational and experimental data provides a strong rationale for the further functional validation of advanced PCa.