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Volume 15
Issue 13
10.3390/cells15131150
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

CRISPRi-Mediated Epigenetic Suppression of TERT Reduces Cell Growth in Non-Small-Cell Lung Cancer Cells

by
Seong-Ho Park
1,†,
Juyoung Hong
2,†,
Woochang Hwang
3,4,*,
Minjeong Kim
5,
Hyeon Jong Yu
6,7,
Taegeun Bae
8,9,
Hyomin K. Lee
8,9,
Ji Yeoun Lee
10,11,12,
Young Chan Lee
5,13,*,
Chul-Kee Park
6,7 and
Junho K. Hur
2,3,9
1
Department of Life Science, College of Natural Sciences, Hanyang University, Seongdong-gu, Seoul 04763, Republic of Korea
2
Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Republic of Korea
3
Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Republic of Korea
4
Department of Pre-Medicine, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea
5
Department of Medicine (AgeTech-Service Convergence Major), College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
6
Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
7
Seoul National University College of Medicine, Seoul 03080, Republic of Korea
8
Hanyang Biomedical Research Institute, Hanyang University, Seoul 04763, Republic of Korea
9
Department of Genetics, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea
10
Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
11
Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul 03080, Republic of Korea
12
Neuroscience Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
13
Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea
 
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*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2026, 15(13), 1150; https://doi.org/10.3390/cells15131150 (registering DOI)
Submission received: 29 April 2026 / Revised: 12 June 2026 / Accepted: 22 June 2026 / Published: 24 June 2026
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Abstract

TERT, the catalytic subunit of telomerase, is aberrantly activated in most cancers and represents an attractive therapeutic target. However, conventional TERT-targeting strategies, including chemical inhibitors and siRNA, are limited by several issues, such as insufficient efficacy and off-target effects. In this study, we investigated whether dCas9-KRAB-mediated CRISPR interference (CRISPRi) could overcome the limitations by transcriptional repression of TERT without DNA cleavage. We first assessed the efficacy of the dCas9-KRAB system by applying it to H1299 non-small-cell lung cancer cells and observed reduction in TERT expression up to approximately 80% and significant decreases in cell viability and growth. Transcriptome-wide analysis showed limited detectable changes in non-target-gene expression under the conditions tested. Together, the results suggest that dCas9-KRAB-mediated CRISPRi could serve as a proof-of-principle approach for targeted repression of TERT in cancer cells with limited detectable effects on non-target-gene expression.
Keywords: TERT; telomerase; CRISPR interference; dCas9-KRAB; transcriptional repression; cancer cells; gene regulation TERT; telomerase; CRISPR interference; dCas9-KRAB; transcriptional repression; cancer cells; gene regulation
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MDPI and ACS Style

Park, S.-H.; Hong, J.; Hwang, W.; Kim, M.; Yu, H.J.; Bae, T.; Lee, H.K.; Lee, J.Y.; Lee, Y.C.; Park, C.-K.; et al. CRISPRi-Mediated Epigenetic Suppression of TERT Reduces Cell Growth in Non-Small-Cell Lung Cancer Cells. Cells 2026, 15, 1150. https://doi.org/10.3390/cells15131150

AMA Style

Park S-H, Hong J, Hwang W, Kim M, Yu HJ, Bae T, Lee HK, Lee JY, Lee YC, Park C-K, et al. CRISPRi-Mediated Epigenetic Suppression of TERT Reduces Cell Growth in Non-Small-Cell Lung Cancer Cells. Cells. 2026; 15(13):1150. https://doi.org/10.3390/cells15131150

Chicago/Turabian Style

Park, Seong-Ho, Juyoung Hong, Woochang Hwang, Minjeong Kim, Hyeon Jong Yu, Taegeun Bae, Hyomin K. Lee, Ji Yeoun Lee, Young Chan Lee, Chul-Kee Park, and et al. 2026. "CRISPRi-Mediated Epigenetic Suppression of TERT Reduces Cell Growth in Non-Small-Cell Lung Cancer Cells" Cells 15, no. 13: 1150. https://doi.org/10.3390/cells15131150

APA Style

Park, S.-H., Hong, J., Hwang, W., Kim, M., Yu, H. J., Bae, T., Lee, H. K., Lee, J. Y., Lee, Y. C., Park, C.-K., & Hur, J. K. (2026). CRISPRi-Mediated Epigenetic Suppression of TERT Reduces Cell Growth in Non-Small-Cell Lung Cancer Cells. Cells, 15(13), 1150. https://doi.org/10.3390/cells15131150

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