Scholarlink

Background <p>Cancer remains a leading cause of global morbidity and mortality, underscoring the need for innovative diagnostic and prognostic biomarkers. PIWI-interacting RNAs (piRNAs) have emerged as critical regulators of gene expression and genomic stability, with increasing evidence linking their dysregulation to oncogenesis. piRNAs can modulate DNA methylation through interactions with DNA methyltransferases (DNMTs), contributing to tumor suppressor gene silencing and broader epigenetic reprogramming. However, the functional implications of piRNA-mediated methylation changes in cancer are not fully elucidated. This study investigates the circulating levels of piR-823 and piR-651, their associations with DNMT3B expression and global DNA methylation, and their correlations with clinical and molecular markers in colorectal, breast, and prostate cancers.</p> Materials and methods <p>A total of 300 participants, including 150 patients with histologically confirmed cancers and 150 age- and sex-matched healthy controls, were enrolled. Plasma piRNA levels were measured via qRT-PCR, while global 5-methylcytosine (5mC) and DNMT3B concentrations were quantified using ELISA. Immunohistochemistry was performed on resected tumor tissues to assess DNMT3B, Ki-67, p53, E-cadherin, vimentin, HER2, and androgen receptor (AR). Correlations were analyzed using Pearson’s test and multivariate regression models. Diagnostic performance was evaluated via Receiver Operating Characteristic (ROC) curves.</p> Results <p>piR-823 was significantly upregulated in colorectal and breast cancers (<i>p</i> &lt; 0.001), while piR-651 was markedly downregulated in prostate cancer (<i>p</i> = 0.002). Cancer patients exhibited elevated levels of DNMT3B and 5mC (both <i>p</i> &lt; 0.001), which correlated strongly with Ki-67 and p53 expression (<i>r</i> &gt; 0.7, <i>p</i> &lt; 0.001). E-cadherin expression was inversely correlated with DNMT3B and piR-823, consistent with a role in epithelial–mesenchymal transition (EMT). cfDNA levels were also significantly elevated in cancer cases (<i>p</i> &lt; 0.001), suggesting potential utility as a non-invasive biomarker.</p> Conclusion <p>The observed associations between piRNA dysregulation, epigenetic markers, and tumor aggressiveness indicators support the potential of circulating piRNAs—particularly piR-823 and piR-651—as novel biomarkers for cancer detection and progression monitoring. These findings warrant further mechanistic studies to validate their functional roles in tumor epigenetics.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Epigenetic functions and biomarker potential of PIWI-interacting RNAs in oncogenesis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月30日

查看全文
  • Kldiashvili Ekaterina,
  • Abiatari Ivane,
  • Kekelia Elene,
  • Iordanishvili Saba,
  • Metreveli Tornike,
  • Dumbadze Eter

摘要

Background

Cancer remains a leading cause of global morbidity and mortality, underscoring the need for innovative diagnostic and prognostic biomarkers. PIWI-interacting RNAs (piRNAs) have emerged as critical regulators of gene expression and genomic stability, with increasing evidence linking their dysregulation to oncogenesis. piRNAs can modulate DNA methylation through interactions with DNA methyltransferases (DNMTs), contributing to tumor suppressor gene silencing and broader epigenetic reprogramming. However, the functional implications of piRNA-mediated methylation changes in cancer are not fully elucidated. This study investigates the circulating levels of piR-823 and piR-651, their associations with DNMT3B expression and global DNA methylation, and their correlations with clinical and molecular markers in colorectal, breast, and prostate cancers.

Materials and methods

A total of 300 participants, including 150 patients with histologically confirmed cancers and 150 age- and sex-matched healthy controls, were enrolled. Plasma piRNA levels were measured via qRT-PCR, while global 5-methylcytosine (5mC) and DNMT3B concentrations were quantified using ELISA. Immunohistochemistry was performed on resected tumor tissues to assess DNMT3B, Ki-67, p53, E-cadherin, vimentin, HER2, and androgen receptor (AR). Correlations were analyzed using Pearson’s test and multivariate regression models. Diagnostic performance was evaluated via Receiver Operating Characteristic (ROC) curves.

Results

piR-823 was significantly upregulated in colorectal and breast cancers (p < 0.001), while piR-651 was markedly downregulated in prostate cancer (p = 0.002). Cancer patients exhibited elevated levels of DNMT3B and 5mC (both p < 0.001), which correlated strongly with Ki-67 and p53 expression (r > 0.7, p < 0.001). E-cadherin expression was inversely correlated with DNMT3B and piR-823, consistent with a role in epithelial–mesenchymal transition (EMT). cfDNA levels were also significantly elevated in cancer cases (p < 0.001), suggesting potential utility as a non-invasive biomarker.

Conclusion

The observed associations between piRNA dysregulation, epigenetic markers, and tumor aggressiveness indicators support the potential of circulating piRNAs—particularly piR-823 and piR-651—as novel biomarkers for cancer detection and progression monitoring. These findings warrant further mechanistic studies to validate their functional roles in tumor epigenetics.