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<p>The role of long non-coding RNAs (lncRNAs) in Natural Killer (NK) cells is still an ongoing research question. LncRNAs are RNAs with a length of more than 200 nucleotides. While they do not code for functional proteins, they have many regulatory roles from transcriptional to post-translational mechanisms that can affect gene expression. On the other hand, NK cells are large, innate, granular immune cells that exert cytotoxic effects against virus-infected and malignant cells using various mechanisms of actions. In this study, we aimed to perform functional analysis of lncRNAs in NK cells. We focused on five lncRNAs: MALAT1, RMRP, LINC-PINT, GAS5, and LINC00299. Our findings revealed that the expressions of the five lncRNAs were downregulated in cultured NK cells and upon cytokine stimulation. In addition, we observed an upregulation of the PD-1 receptor on the surface of NK cells in response to knocking down RMRP. This suggests that RMRP may have an inhibitory effect on PD-1 expression in NK cells. The proposed inverse relationship between RMRP and PD-1 offers new insights into the regulation of PD-1 expression and its role in NK cell function. Given PD-1’s critical role as an immune checkpoint, by understanding the regulatory relationship between RMRP and PD-1, new strategies can be explored to enhance NK cell efficacy, opening up new possibilities for designing immunotherapies that restore NK cell function by potentially targeting PD-1 regulation.</p>

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LncRNA RMRP knockdown upregulates PD-1 expression in natural killer cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月3日

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  • Sarah Abouhegaziah,
  • Doris Urlaub,
  • Ahmed Moustafa,
  • Maha Mostafa,
  • Amged Ouf,
  • Khaled Abou-Aisha,
  • Carsten Watzl,
  • Mona Rady

摘要

The role of long non-coding RNAs (lncRNAs) in Natural Killer (NK) cells is still an ongoing research question. LncRNAs are RNAs with a length of more than 200 nucleotides. While they do not code for functional proteins, they have many regulatory roles from transcriptional to post-translational mechanisms that can affect gene expression. On the other hand, NK cells are large, innate, granular immune cells that exert cytotoxic effects against virus-infected and malignant cells using various mechanisms of actions. In this study, we aimed to perform functional analysis of lncRNAs in NK cells. We focused on five lncRNAs: MALAT1, RMRP, LINC-PINT, GAS5, and LINC00299. Our findings revealed that the expressions of the five lncRNAs were downregulated in cultured NK cells and upon cytokine stimulation. In addition, we observed an upregulation of the PD-1 receptor on the surface of NK cells in response to knocking down RMRP. This suggests that RMRP may have an inhibitory effect on PD-1 expression in NK cells. The proposed inverse relationship between RMRP and PD-1 offers new insights into the regulation of PD-1 expression and its role in NK cell function. Given PD-1’s critical role as an immune checkpoint, by understanding the regulatory relationship between RMRP and PD-1, new strategies can be explored to enhance NK cell efficacy, opening up new possibilities for designing immunotherapies that restore NK cell function by potentially targeting PD-1 regulation.