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<p>Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, driven by both modifiable factors (lifestyle and environment) and non-modifiable factors (age and genetics). Increasing evidence highlights epigenetic dysregulation as a key mechanism in CRC initiation and progression, emphasizing the need for reliable molecular biomarkers for early detection and prognosis. In this study, we investigated the expression profiles of key long non-coding RNAs (lncRNAs)—<i>CCAT-1</i>, <i>EPHA7</i>, and <i>NBAT-1</i>—and microRNAs (miRNAs)—<i>miR-21</i>, <i>miR-372</i>, <i>miR-760</i>, and <i>miR-145</i>—in an Egyptian cohort comprising 390 CRC patients and 180 healthy controls. Patients were classified into stages I–IV, and biochemical parameters were assessed. Gene expression levels were quantified using SYBR Green real-time qPCR to evaluate their diagnostic and prognostic relevance across disease stages. Our results revealed a consistent epigenetic pattern associated with CRC progression. <i>CCAT-1</i> and <i>EPHA7</i> were significantly upregulated in CRC patients, whereas <i>NBAT-1</i> was markedly downregulated across all stages (I–IV). Among miRNAs, <i>miR-21</i> and <i>miR-372</i> showed significant upregulation in specific stages, while <i>miR-760</i> and <i>miR-145</i> were consistently downregulated compared with controls. Additionally, Chitinase-3-like protein 1 (YKL-40) was significantly elevated in CRC patients, particularly in advanced stages (III and IV), indicating its association with tumor aggressiveness. Collectively, these findings demonstrate that a combined panel of <i>CCAT-1</i>, <i>EPHA7</i>, <i>NBAT-1</i>, <i>miR-21</i>, <i>miR-372</i>, <i>miR-760</i>, <i>miR-145</i>, and YKL-40 may serve as a powerful diagnostic and prognostic tool in CRC. This multi-marker signature offers improved potential for early detection, disease stratification, and clinical monitoring in CRC patients.</p>

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Epigenetic Modulation of Long Noncoding RNAs and MicroRNAs in Colorectal Cancer Susceptibility

  • 期刊论文

  • 发表日期：

    2026年7月22日

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  • Abeer Mogadem,
  • Ahmed A. Abd-Rabou,
  • Olfat G. Shaker,
  • Shimos A. Alshareef,
  • Ghada Ayeldeen

摘要

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, driven by both modifiable factors (lifestyle and environment) and non-modifiable factors (age and genetics). Increasing evidence highlights epigenetic dysregulation as a key mechanism in CRC initiation and progression, emphasizing the need for reliable molecular biomarkers for early detection and prognosis. In this study, we investigated the expression profiles of key long non-coding RNAs (lncRNAs)—CCAT-1, EPHA7, and NBAT-1—and microRNAs (miRNAs)—miR-21, miR-372, miR-760, and miR-145—in an Egyptian cohort comprising 390 CRC patients and 180 healthy controls. Patients were classified into stages I–IV, and biochemical parameters were assessed. Gene expression levels were quantified using SYBR Green real-time qPCR to evaluate their diagnostic and prognostic relevance across disease stages. Our results revealed a consistent epigenetic pattern associated with CRC progression. CCAT-1 and EPHA7 were significantly upregulated in CRC patients, whereas NBAT-1 was markedly downregulated across all stages (I–IV). Among miRNAs, miR-21 and miR-372 showed significant upregulation in specific stages, while miR-760 and miR-145 were consistently downregulated compared with controls. Additionally, Chitinase-3-like protein 1 (YKL-40) was significantly elevated in CRC patients, particularly in advanced stages (III and IV), indicating its association with tumor aggressiveness. Collectively, these findings demonstrate that a combined panel of CCAT-1, EPHA7, NBAT-1, miR-21, miR-372, miR-760, miR-145, and YKL-40 may serve as a powerful diagnostic and prognostic tool in CRC. This multi-marker signature offers improved potential for early detection, disease stratification, and clinical monitoring in CRC patients.