CRISPR-dCas9 in Cancer Epigenetic Therapy Progress
DOI:
https://doi.org/10.61173/d53knt23Keywords:
-CRISPR-dCas9, Cancer, Epigenetics, gene editing, Tumor immunityAbstract
Cancer appears and develops not only related to genes but also takes an important role in epigenetic regulation. In recent years, CRISPR-dCas9 as a new precision gene-editing tool has aroused much attention because it can combine with epigenetic effectors to regulate cancer-related genes specifically. It shows great prospects for treating a wide variety of diseases, particularly for epigenetic modifications of cancer. This article reviews the biochemistry of CRISPR-dCas9 systems and their use in epigenetic modification of cancer, focusing on how DNA methylation, histone modification, etc., affect tumorigenesis. In addition, the recent progress, challenges, and prospects of CRISPR-dCas9 mediated epigenetic editing technology for cancer gene therapy are also presented. By analyzing the current problems encountered in the clinical translation of CRISPR-dCas9 technology, this article has shown that CRISPR-dCas9 technology has the potential to become a targeted cancer treatment, which can also provide references for future medical research.
References
[1] Bourgeois W, Armstrong SA, Heikamp EB, “Epigenetic Therapies,” Cold Spring Harb Perspect Med, published online Dec. 18, 2024.
[2] Yang W, Yan J, Zhuang P, et al., “Progress of delivery methods for CRISPR-Cas9,” Expert Opin Drug Deliv, vol. 19, no. 8, pp. 913–926, 2022.
[3] Ul Haq SI, Zheng D, Feng N, et al., “Progresses of CRISPR/ Cas9 genome editing in forage crops,” J Plant Physiol, vol. 279, p. 153860, 2022.
[4] Yin W, Chen Z, Huang J, et al., “Application of CRISPR- Cas9 gene editing technology in crop breeding,” Sheng Wu Gong Cheng Xue Bao, vol. 39, no. 2, pp. 399–424, 2023.
[5] Cui YR, Wang SJ, Ma T, et al., “KPT330 improves Cas9 precision genome- and base-editing by selectively regulating mRNA nuclear export,” Commun Biol, vol. 5, no. 1, p. 237, Mar. 2022.
[6] Javaid N, Pham TLH, Choi S, “Functional Comparison between VP64-dCas9-VP64 and dCas9-VP192 CRISPR Activators in Human Embryonic Kidney Cells,” Int J Mol Sci, vol. 22, no. 1, 2021.
[7] Rahman MM, Tollefsbol TO, “Targeting cancer epigenetics with CRISPR-dCAS9: Principles and prospects,” Methods, vol. 187, pp. 77–91, 2020.
[8] Hosseinpour M, Xi X, Liu L, et al., “SAM-DNMT3A, a strategy for induction of genome-wide DNA methylation, identifies DNA methylation as a vulnerability in ER-positive breast cancers,” Nat Commun, vol. 15, no. 1, p. 10449, 2024.
[9] Kocak O, Kankaya S, Kalender G, Citgez S, Onal B, Dincer Y, “Determination of global DNA methylation level by methylation-sensitive comet assay in patients with urinary bladder cancer,” Mutagenesis, vol. 39, no. 6, pp. 280–286, 2024.
[10] Atsumi G, Matsuo K, Fukuzawa N, Matsumura T, “Virus- Mediated Targeted DNA Methylation Illuminates the Dynamics of Methylation in an Endogenous Plant Gene,” Int J Mol Sci, vol. 22, no. 8, 2021.
[11] Nanavaty V, Abrash EW, Hong C, et al., “DNA Methylation Regulates Alternative Polyadenylation via CTCF and the Cohesin Complex,” Mol Cell, vol. 78, no. 4, pp. 752–764.e6, 2020.
[12] Lian Y, Hao H, Xu J, Bo T, Wang W, “Histone Chaperone Nrp1 Mutation Affects the Acetylation of H3K56 in Tetrahymena thermophila,” Cells, vol. 11, no. 3, 2022.
[13] Ma Y, Lv W, Guo Y, et al., “Histone demethylases in autophagy and inflammation,” Cell Commun Signal, vol. 23, no. 1, p. 24, 2025.
[14] Yin X, Li J, Zhao J, Zheng W, Zhang A, Ma J, “Epigenetic modifications involving ncRNAs in digestive system cancers: focus on histone modification,” Clin Epigenetics, vol. 16, no. 1, p. 162, 2024.
[15] Wu D, Qiu Y, Jiao Y, Qiu Z, Liu D, “Small Molecules Targeting HATs, HDACs, and BRDs in Cancer Therapy,” Front Oncol, vol. 10, p. 560487, 2020.
[16] Rahimian N, Sheida A, Rajabi M, et al., “Non-coding RNAs and exosomal non-coding RNAs in pituitary adenoma,” Pathol Res Pract, vol. 248, p. 154649, 2023.
[17] Fadaei S, Zarepour F, Parvaresh M, et al., “Epigenetic regulation in myocardial infarction: Non-coding RNAs and exosomal non-coding RNAs,” Front Cardiovasc Med, vol. 9, p. 1014961, 2022.
[18] Lulli M, Napoli C, Landini I, Mini E, Lapucci A, “Role of Non-Coding RNAs in Colorectal Cancer: Focus on Long Non- Coding RNAs,” Int J Mol Sci, vol. 23, no. 21, 2022.
[19] Wang Y, Wang H, Shao W, et al., “Large-scale loss-offunction perturbations reveal a comprehensive epigenetic Dean&Francis ISSN 2959-409X regulatory network in breast cancer,” Cancer Biol Med, vol. 21, no. 1, 2023.
[20] Zhang M, Hu T, Ma T, Huang W, Wang Y, “Epigenetics and environmental health,” Front Med, vol. 18, no. 4, pp. 571–596, 2024.
[21] Guerra-Resendez RS, Lydon SL, Ma AJ, et al., “Characterization of Rationally Designed CRISPR/Cas9-Based DNA Methyltransferases with Distinct Methyltransferase and Gene Silencing Activities in Human Cell Lines and Primary Human T Cells,” ACS Synth Biol, vol. 14, no. 2, pp. 384–397, 2025.
[22] Zapanta Rinonos S, Li T, Pianka ST, et al., “dCas9/ CRISPR-based methylation of O-6-methylguanine-DNA methyltransferase enhances chemosensitivity to temozolomide in malignant glioma,” J Neurooncol, vol. 166, no. 1, pp. 129–142, 2024.
[23] Sarno F, Goubert D, Logie E, et al., “Functional Validation of the Putative Oncogenic Activity of PLAU,” Biomedicines, vol. 11, no. 1, 2022.
[24] Wilk C, Effenberg L, Abberger H, et al., “CRISPR/Cas9- mediated demethylation of FOXP3-TSDR toward Tregcharacteristic programming of Jurkat T cells,” Cell Immunol, vol. 371, p. 104471, 2021.
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