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Print ISSN: 1792-1074 Online ISSN: 1792-1082
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February-2026 Volume 31 Issue 2

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Article Open Access

Genome‑wide CRISPR screening identifies CLDN1 as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer

  • Authors:
    • Xiaogang Wang
    • Benzhong Mi
    • Jinfeng Lv
    • Xin Tang
    • Jingyu Huang
    • Fei Liu
    • Yajing Xing
    • Xingjian Wen
    • Yongde Wang
    • Yadong Zhong

  • View Affiliations / Copyright

    Affiliations: Chongqing Key Laboratory of Chinese Medicine and Health Science, Chongqing Academy of Chinese Materia Medica, Chongqing 400065, P.R. China, Institute for Silk and Related Biomaterials Research, Chongqing Academy of Animal Sciences, Chongqing 402460, P.R. China, School of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, P.R. China, School of Basic Medical Sciences, Chongqing University of Chinese Medicine, Chongqing 402760, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 62
    |
    Published online on: December 1, 2025
       https://doi.org/10.3892/ol.2025.15415
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Abstract

Berberine (BBR), a natural compound with diverse anticancer properties, exerts potent inhibitory effects on lung cancer cell proliferation. However, its particular molecular targets remain unknown. The present study aimed to identify the key genetic determinants that mediate the cellular response to BBR in lung cancer. To achieve this, genome‑wide clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‑associated protein 9 (Cas9) knockout screening was conducted in A549 cells, followed by functional validation and mechanistic assays. In the study, the genome‑wide CRISPR/Cas9 knockout screening in A549 lung cancer cells identified claudin‑1 (CLDN1) as a critical modulator of BBR sensitivity. Notably, whilst CLDN1 was enriched in the positive selection screen, its knockout markedly increased the sensitivity of A549 cells to BBR, thus leading to enhanced G1‑phase arrest and reduced proliferation. These findings suggest that CLDN1 could serve a dual role, promoting cellular resistance under selective pressure, while simultaneously demonstrating a therapeutic vulnerability when directly inhibited. Overall, the present study identified CLDN1 as a key mediator of the anticancer effects of BBR, thus providing a foundation for its potential development as a therapeutic target to optimize lung cancer therapy.

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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Mi B, Lv J, Tang X, Huang J, Liu F, Xing Y, Wen X, Wang Y, Zhong Y, Zhong Y, et al: Genome‑wide CRISPR screening identifies <em>CLDN1</em> as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer. Oncol Lett 31: 62, 2026.
APA
Wang, X., Mi, B., Lv, J., Tang, X., Huang, J., Liu, F. ... Zhong, Y. (2026). Genome‑wide CRISPR screening identifies <em>CLDN1</em> as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer. Oncology Letters, 31, 62. https://doi.org/10.3892/ol.2025.15415
MLA
Wang, X., Mi, B., Lv, J., Tang, X., Huang, J., Liu, F., Xing, Y., Wen, X., Wang, Y., Zhong, Y."Genome‑wide CRISPR screening identifies <em>CLDN1</em> as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer". Oncology Letters 31.2 (2026): 62.
Chicago
Wang, X., Mi, B., Lv, J., Tang, X., Huang, J., Liu, F., Xing, Y., Wen, X., Wang, Y., Zhong, Y."Genome‑wide CRISPR screening identifies <em>CLDN1</em> as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer". Oncology Letters 31, no. 2 (2026): 62. https://doi.org/10.3892/ol.2025.15415
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Mi B, Lv J, Tang X, Huang J, Liu F, Xing Y, Wen X, Wang Y, Zhong Y, Zhong Y, et al: Genome‑wide CRISPR screening identifies <em>CLDN1</em> as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer. Oncol Lett 31: 62, 2026.
APA
Wang, X., Mi, B., Lv, J., Tang, X., Huang, J., Liu, F. ... Zhong, Y. (2026). Genome‑wide CRISPR screening identifies <em>CLDN1</em> as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer. Oncology Letters, 31, 62. https://doi.org/10.3892/ol.2025.15415
MLA
Wang, X., Mi, B., Lv, J., Tang, X., Huang, J., Liu, F., Xing, Y., Wen, X., Wang, Y., Zhong, Y."Genome‑wide CRISPR screening identifies <em>CLDN1</em> as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer". Oncology Letters 31.2 (2026): 62.
Chicago
Wang, X., Mi, B., Lv, J., Tang, X., Huang, J., Liu, F., Xing, Y., Wen, X., Wang, Y., Zhong, Y."Genome‑wide CRISPR screening identifies <em>CLDN1</em> as a central node in the anticancer mechanisms of berberine and as a therapeutic target in lung cancer". Oncology Letters 31, no. 2 (2026): 62. https://doi.org/10.3892/ol.2025.15415
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