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<p>Cervical cancer remains a major cause of cancer-related mortality in women, and there is limited understanding of strand-specific miRNA regulation. This study investigated the differential regulatory roles of miR-21-5p and miR-21-3p and their associated gene networks using an integrative computational approach. A total of 664 experimentally validated targets for miR-21-5p and 3663 for miR-21-3p were identified, with 628 and 99 strand-specific targets, respectively, and five overlapping genes (<i>SPRY1</i>, <i>STAT3</i>, <i>CLIP4</i>, <i>SMAD7</i>, and <i>PPARA</i>). Expression analysis using TCGA-CESC data demonstrated consistent upregulation of miR-21 across all clinical subgroups, independent of age, stage, and histological subtypes. Protein–protein interaction analysis revealed a dense network for miR-21-5p (559 nodes, 3252 edges) compared to that for miR-21-3p (4 nodes, 133 edges), indicating a broader regulatory influence of the 5p strand. Five hub genes (<i>TP53</i>, <i>PTEN</i>, <i>EGFR</i>, <i>STAT3</i>, and <i>CCND1</i>) were identified, with <i>PTEN</i> and <i>EGFR</i> common to both strands. Differential expression analysis showed downregulation of <i>PTEN</i> and upregulation of <i>CCND1</i>, <i>EGFR</i> (<i>p</i> = 1.83 × 10⁻<sup>5</sup>), <i>STAT3</i>, and <i>TP53</i> in the tumor tissues. Only <i>EGFR</i> demonstrated a significant association with overall survival, while the others require further validation. Functional enrichment analysis highlighted pathways related to cell cycle regulation, apoptosis, and oncogenic signaling. Molecular docking further identified potential drug candidates with favorable binding affinities for the key hub proteins. These findings suggest a potential regulatory role for miR-21 strands and highlight <i>PTEN</i> and <i>EGFR</i> as central nodes, providing a computational framework for prioritizing potential therapeutic targets in cervical cancer.</p>

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Identification of miR-21-5p and miR-21-3p regulated hub genes and drug repurposing targets in cervical cancer: an integrative computational analysis

  • 期刊论文

  • 发表日期：

    2026年7月21日

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  • Muhammad Bilal Azmi,
  • Rafia Wasi,
  • Arisha Sohail,
  • Uzma Asif

摘要

Cervical cancer remains a major cause of cancer-related mortality in women, and there is limited understanding of strand-specific miRNA regulation. This study investigated the differential regulatory roles of miR-21-5p and miR-21-3p and their associated gene networks using an integrative computational approach. A total of 664 experimentally validated targets for miR-21-5p and 3663 for miR-21-3p were identified, with 628 and 99 strand-specific targets, respectively, and five overlapping genes (SPRY1, STAT3, CLIP4, SMAD7, and PPARA). Expression analysis using TCGA-CESC data demonstrated consistent upregulation of miR-21 across all clinical subgroups, independent of age, stage, and histological subtypes. Protein–protein interaction analysis revealed a dense network for miR-21-5p (559 nodes, 3252 edges) compared to that for miR-21-3p (4 nodes, 133 edges), indicating a broader regulatory influence of the 5p strand. Five hub genes (TP53, PTEN, EGFR, STAT3, and CCND1) were identified, with PTEN and EGFR common to both strands. Differential expression analysis showed downregulation of PTEN and upregulation of CCND1, EGFR (p = 1.83 × 10⁻5), STAT3, and TP53 in the tumor tissues. Only EGFR demonstrated a significant association with overall survival, while the others require further validation. Functional enrichment analysis highlighted pathways related to cell cycle regulation, apoptosis, and oncogenic signaling. Molecular docking further identified potential drug candidates with favorable binding affinities for the key hub proteins. These findings suggest a potential regulatory role for miR-21 strands and highlight PTEN and EGFR as central nodes, providing a computational framework for prioritizing potential therapeutic targets in cervical cancer.