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Background <p>Lung cancer is the leading cause of cancer-related mortality worldwide; however, despite the development and clinical application of various drugs, the prognosis remains poor. One reason for this is the high rate of recurrence and metastasis. The cancer stem cell (CSC) theory has been proposed to explain their root cause, and removal of CSCs is necessary to cure cancer completely; however, detailed profiles of lung CSCs have not been clarified. Here, we used single-cell RNA sequencing (scRNA-seq) data to identify novel markers for lung CSCs and validated their expression and function in vitro.</p> Methods <p>A549-derived tumorspheres were used as a model for lung CSCs. To identify genes upregulated in CSC-like cells, we reanalyzed two publicly available scRNA-seq datasets from human lung cancer tissues. Additionally, trajectory analysis was performed to examine changes in candidate gene expression during CSC differentiation. The role of these candidate genes in CSC regulation was further investigated through functional assays.</p> Results <p>Tumorspheres exhibited increased expression of well-established CSC markers. scRNA-seq analysis suggested that <i>SIGMAR1</i> expression was significantly upregulated in CSC-like cells and decreased with differentiation. Furthermore, siRNA-mediated <i>SIGMAR1</i> knockdown suppressed tumorsphere self-renewal capacity and reduced CSC marker expression.</p> Conclusions <p>We propose that SIGMAR1 serves as a potential functional marker of CSCs and plays a crucial role in regulating self-renewal capacity. Targeting SIGMAR1 may provide a novel therapeutic strategy for preventing metastasis and recurrence—major clinical challenges in lung cancer treatment. Future studies should investigate the underlying mechanisms by which SIGMAR1 modulates CSC properties.</p>

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In silico-based analysis and in vitro experiments identify SIGMAR1 as a potential marker of putative lung cancer stem cells

  • 期刊论文

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  • 发表日期：

    2025年4月26日

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  • Tetsuhiro Horie,
  • Ayane Kuwano,
  • Takuya Sakamoto,
  • Yuka Nakamura,
  • Kayoko Yamaguchi,
  • Ikuhiro Tanida,
  • Satoshi Osawa,
  • Kazuo Yasumoto,
  • Yasuhito Ishigaki

摘要

Background

Lung cancer is the leading cause of cancer-related mortality worldwide; however, despite the development and clinical application of various drugs, the prognosis remains poor. One reason for this is the high rate of recurrence and metastasis. The cancer stem cell (CSC) theory has been proposed to explain their root cause, and removal of CSCs is necessary to cure cancer completely; however, detailed profiles of lung CSCs have not been clarified. Here, we used single-cell RNA sequencing (scRNA-seq) data to identify novel markers for lung CSCs and validated their expression and function in vitro.

Methods

A549-derived tumorspheres were used as a model for lung CSCs. To identify genes upregulated in CSC-like cells, we reanalyzed two publicly available scRNA-seq datasets from human lung cancer tissues. Additionally, trajectory analysis was performed to examine changes in candidate gene expression during CSC differentiation. The role of these candidate genes in CSC regulation was further investigated through functional assays.

Results

Tumorspheres exhibited increased expression of well-established CSC markers. scRNA-seq analysis suggested that SIGMAR1 expression was significantly upregulated in CSC-like cells and decreased with differentiation. Furthermore, siRNA-mediated SIGMAR1 knockdown suppressed tumorsphere self-renewal capacity and reduced CSC marker expression.

Conclusions

We propose that SIGMAR1 serves as a potential functional marker of CSCs and plays a crucial role in regulating self-renewal capacity. Targeting SIGMAR1 may provide a novel therapeutic strategy for preventing metastasis and recurrence—major clinical challenges in lung cancer treatment. Future studies should investigate the underlying mechanisms by which SIGMAR1 modulates CSC properties.