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Background <p>Copper-induced cell death, where copper induces cytotoxicity to kill cancer cells, exerts an unclear role in colorectal cancer. This study aimed to identify lncRNAs co-expressed with CICD-related genes and explore their effect on CRC.</p> Methods <p>Differentially expressed lncRNAs between CRC and normal samples were identified from public datasets, followed by co-expression analysis of 10 CICD-related genes. The prognostic lncRNA signatures were used to construct a prognostic model and validated by Kaplan–Meier and ROC curves. Clinical feature analysis and immune microenvironment assessment of identified lncRNAs were conducted, and in vitro assays were performed to validate their expression pattern and effect in CRC.</p> Results <p>Five lncRNAs co-expressed with CICD-related genes were identified, correlating with overall survival. The prognostic model showed that low-risk patients had better outcomes and higher CICD related gene expression, suggesting copper toxicity may eliminate CRC cells. Additionally, immune microenvironment analysis revealed that the low-risk group had higher immune cell infiltration along with upregulated immune checkpoint and HLA gene expression, indicating that CICD-related lncRNAs may influence CRC progression through immune microenvironment regulation. In vitro studies revealed the elevated levels of SNHG7 in CRC cells, and inhibiting SNHG7 suppressed CRC proliferation, migration, and invasion. SNHG7 downregulation also increased FDX1 expression, a key protein in the cuproptosis pathway.</p> Conclusions <p>Five lncRNAs were identified as prognostic markers in CRC, with SNHG7 promoting CRC via a copper-dependent pathway. These findings provide insights for developing copper-targeted therapies for CRC patients.</p>

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Long non-coding RNA SNHG7 as a key driver of colorectal cancer proliferation and metastasis by inhibiting cuproptosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月2日

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  • Xin Guo,
  • Xinyi He,
  • Weitao Chen,
  • Jianlong Zhou,
  • Zejian Lyu,
  • Zhou Li,
  • Yong Li

摘要

Background

Copper-induced cell death, where copper induces cytotoxicity to kill cancer cells, exerts an unclear role in colorectal cancer. This study aimed to identify lncRNAs co-expressed with CICD-related genes and explore their effect on CRC.

Methods

Differentially expressed lncRNAs between CRC and normal samples were identified from public datasets, followed by co-expression analysis of 10 CICD-related genes. The prognostic lncRNA signatures were used to construct a prognostic model and validated by Kaplan–Meier and ROC curves. Clinical feature analysis and immune microenvironment assessment of identified lncRNAs were conducted, and in vitro assays were performed to validate their expression pattern and effect in CRC.

Results

Five lncRNAs co-expressed with CICD-related genes were identified, correlating with overall survival. The prognostic model showed that low-risk patients had better outcomes and higher CICD related gene expression, suggesting copper toxicity may eliminate CRC cells. Additionally, immune microenvironment analysis revealed that the low-risk group had higher immune cell infiltration along with upregulated immune checkpoint and HLA gene expression, indicating that CICD-related lncRNAs may influence CRC progression through immune microenvironment regulation. In vitro studies revealed the elevated levels of SNHG7 in CRC cells, and inhibiting SNHG7 suppressed CRC proliferation, migration, and invasion. SNHG7 downregulation also increased FDX1 expression, a key protein in the cuproptosis pathway.

Conclusions

Five lncRNAs were identified as prognostic markers in CRC, with SNHG7 promoting CRC via a copper-dependent pathway. These findings provide insights for developing copper-targeted therapies for CRC patients.