medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2025.03.3-13medgen-2622Research ArticleНАУЧНЫЙ ОБЗОРREVIEWРоль микроРНК в патогенезе и терапии онкологических заболеванийThe role of microRNAs in the pathogenesis and therapy of oncological diseasesОмаровМ. А.OmarovM. A.

Омаров Магомед Абдурахманович

197022, г. Санкт-Петербург, ул. Льва Толстого, д. 6-8

Magomed A. Omarov

6-8, L’va Tolstogo st., Saint Petersburg, 197022

sic_mundus@mail.ruГаджиевР. М.GadjievR. M.

450008, г. Уфа, Республика Башкортостан, ул. Ленина, д. 3

3, Lenina st., Ufa, 450008

АхматнуровА. Р.AkhmatnurovA. R.

450008, г. Уфа, Республика Башкортостан, ул. Ленина, д. 3

3, Lenina st., Ufa, 450008

МусаеваМ. Х.MusaevaM. H.

450008, г. Уфа, Республика Башкортостан, ул. Ленина, д. 3

3, Lenina st., Ufa, 450008

ЗиякаевЛ. В.MusaevaM. H.

450008, г. Уфа, Республика Башкортостан, ул. Ленина, д. 3

3, Lenina st., Ufa, 450008

РасуловМ. Р.RasulovM. R.

450008, г. Уфа, Республика Башкортостан, ул. Ленина, д. 3

3, Lenina st., Ufa, 450008

АбдуллинР. Ф.RasulovM. R.

450008, г. Уфа, Республика Башкортостан, ул. Ленина, д. 3

3, Lenina st., Ufa, 450008

ФГБОУ ВО Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова Министерства здравоохранения Российской ФедерацииРоссияI.P. Pavlov First Saint Petersburg State Medical UniversityRussian FederationФГБОУ ВО Башкирский Государственный Медицинский Университет Министерства здравоохранения Российской ФедерацииРоссияBashkir State Medical UniversityRussian Federation202512052025243313Copyright © Омаров М.А., Гаджиев Р.М., Ахматнуров А.Р., Мусаева М.Х., Зиякаев Л.В., Расулов М.Р., Абдуллин Р.Ф., 20252025Омаров М.А., Гаджиев Р.М., Ахматнуров А.Р., Мусаева М.Х., Зиякаев Л.В., Расулов М.Р., Абдуллин Р.Ф.Omarov M.A., Gadjiev R.M., Akhmatnurov A.R., Musaeva M.H., Musaeva M.H., Rasulov M.R., Rasulov M.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2622

Введение. МикроРНК (miRNA) – это класс коротких некодирующих молекул РНК, играющих центральную роль в посттранскрипционной регуляции экспрессии генов. Эти молекулы участвуют в ключевых клеточных процессах, таких как пролиферация, апоптоз, дифференцировка и ангиогенез, что делает их важными регуляторами клеточного гомеостаза. В зависимости от контекста микроРНК могут выступать как онкогены или супрессоры опухолей, регулируя сигнальные пути, связанные с развитием и прогрессией злокачественных новообразований, включая PI3K/AKT и Wnt/β-катенин.Цель: провести комплексный анализ роли микроРНК в патогенезе и терапии онкологических заболеваний.Результаты. Рассмотрены перспективы применения микроРНК как биомаркеров для ранней диагностики, таких как miR-21 при раке поджелудочной железы и miR-141 при раке предстательной железы. Приводятся результаты доклинических и клинических исследований, демонстрирующих терапевтический потенциал микроРНК, включая использование AntagomiR-21 и мимиков miR-34a (MRX34). Также освещены вызовы, связанные с доставкой и биобезопасностью, и возможные пути их решения с помощью нанотехнологий. Обсуждаются молекулярные механизмы их участия в опухолевой прогрессии, диагностический потенциал и возможности терапевтического применения. Особое внимание уделено современным достижениям, включая использование технологий NGS для профилирования микроРНК и CRISPR/Cas9 для их функционального анализа.Заключение. Полученные данные подтверждают, что микроРНК являются перспективным направлением в диагностике и лечении онкологических заболеваний. Продолжение исследований в этой области может значительно улучшить понимание молекулярных механизмов канцерогенеза и привести к разработке персонализированных подходов к терапии.

Introduction. MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that play a central role in the post-transcriptional regulation of gene expression. These molecules are involved in key cellular processes such as proliferation, apoptosis, differentiation, and angiogenesis, making them crucial regulators of cellular homeostasis. Depending on the context, miRNAs can act as oncogenes or tumor suppressors, regulating signaling pathways associated with the development and progression of malignancies, including the PI3K/AKT and Wnt/β-catenin pathways.Aim: to provide a comprehensive analysis of the role of miRNAs in the pathogenesis and therapy of oncological diseases.Results. The article explores the potential of miRNAs as biomarkers for early diagnosis, such as miR-21 in pancreatic cancer and miR-141 in prostate cancer. It also highlights findings from preclinical and clinical studies demonstrating the therapeutic potential of miRNAs, including the use of AntagomiR-21 and miR-34a mimics (MRX34). Challenges related to delivery and biosafety are also addressed, with potential solutions proposed through the application of nanotechnology. The molecular mechanisms of their involvement in tumor progression, their diagnostic potential, and therapeutic applications are discussed. Special attention is given to recent advancements, including the use of next-generation sequencing (NGS) for miRNA profiling and CRISPR/Cas9 for functional analysis.Conclusions. The findings confirm that miRNAs represent a promising direction in the diagnosis and treatment of oncological diseases. Continued research in this field could significantly enhance our understanding of the molecular mechanisms underlying cancer and lead to the development of personalized therapeutic approaches.

микроРНКканцерогенезтаргетная терапияCRISPR/Casгенная инженерияиммунотерапиябиомаркерыmicroRNAscarcinogenesistargeted therapyCRISPR/Casgenetic engineeringimmunotherapybiomarkersReferencesO’Brien J., Hayder H., Zayed Y., Peng,C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Frontiers in endocrinology. 2018; 9: 402. https://doi.org/10.3389/fendo.2018.00402.O’Brien J., Hayder H., Zayed Y., Peng,C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Frontiers in endocrinology. 2018;9: 402. https://doi.org/10.3389/fendo.2018.00402.Омаров М.А., Мулюков А.Р., Халитов Р.В., и др. Эпигенетическая модуляция в медицине: регуляция генной экспрессии в контексте патогенеза и терапии. Acta biomedica scientifica. 2024; 9(6): 22-33.Omarov M.A., Mulyukov A.R., Khalitov R.V., et al. Epigeneticheskaya modulyatsiya v meditsine: regulyatsiya gennoy ekspressii v kontekste patogeneza i terapii. [Epigenetic modulation in medicine: Regulation of gene expression in the context of pathogenesis and therapy]. Acta biomedica scientifica. 2024; 9(6): 22-33. (In Russ.) doi: 10.29413/ABS.2024-9.6.3.Sung H., Ferlay J., Siegel R.L., et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. https://doi.org/10.3322/caac.21660.Sung H., Ferlay J., Siegel R.L., et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. https://doi.org/10.3322/caac.21660.Shi Y., Liu Z., Lin Q., et al. MiRNAs and Cancer: Key Link in Diagnosis and Therapy. Genes (Basel). 2021;12(8):1289. https://doi.org/10.3390/genes12081289.Shi Y., Liu Z., Lin Q., et al. MiRNAs and Cancer: Key Link in Diagnosis and Therapy. Genes (Basel). 2021;12(8):1289. https://doi.org/10.3390/genes12081289.Kwon Y., Kim M., Kim Y., Jung H.S., Jeoung D. Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages. Front Immunol. 2020;11:1167. https://doi.org/10.3389/fimmu.2020.01167.Kwon Y., Kim M., Kim Y., Jung H.S., Jeoung D. Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages. Front Immunol. 2020;11:1167. https://doi.org/10.3389/fimmu.2020.01167.Мирошниченко С.К., Патутина О.А., Зенкова М.А. МикроРНК-направленные олигонуклеотидные конструкции с различным механизмом действия для эффективного подавления процессов канцерогенеза. БИОпрепараты. Профилактика, диагностика, лечение. 2024; 24(2): 140-156.Miroshnichenko S.K., Patutina O.A., Zenkova M.A. MikroRNK-napravlennyye oligonukleotidnyye konstruktsii s razlichnym mekhanizmom deystviya dlya effektivnogo podavleniya protsessov kantserogeneza [miRNA-targeting oligonucleotide constructs with various mechanisms of action as effective inhibitors of carcinogenesis]. BIOpreparaty. Profilaktika, diagnostika, lecheniye [Biological Products. Prevention, Diagnosis, Treatment]. 2024;24(2):140-156. (In Russ.) https://doi.org/10.30895/2221-996X-2024-24-2-140-156Treiber T., Treiber N., Meister G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nature Reviews Molecular Cell Biology. 2018;20:5 - 20. https://doi.org/10.1038/s41580-018-0059-1.Treiber T., Treiber N., Meister G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nature Reviews Molecular Cell Biology. 2018;20:5 - 20. https://doi.org/10.1038/s41580-018-0059-1.Bibel B., Elkayam E., Silletti S., Komives E.A., Joshua-Tor L. Target binding triggers hierarchical phosphorylation of human Argonaute-2 to promote target release. Elife. 2022;11:e76908. https://doi.org/10.7554/eLife.76908.Bibel B., Elkayam E., Silletti S., Komives E.A., Joshua-Tor L. Target binding triggers hierarchical phosphorylation of human Argonaute-2 to promote target release. Elife. 2022;11:e76908. https://doi.org/10.7554/eLife.76908.Annese T., Tamma R., De Giorgis M., Ribatti D. microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis. Front Oncol. 2020;10:581007. https://doi.org/10.3389/fonc.2020.581007.Annese T., Tamma R., De Giorgis M., Ribatti D. microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis. Front Oncol. 2020;10:581007. https://doi.org/10.3389/fonc.2020.581007.Maraghechi P., Aponte M.T.S., Ecker A., et al. Pluripotency-Associated microRNAs in Early Vertebrate Embryos and Stem Cells. Genes (Basel). 2023;14(7):1434. https://doi.org/10.3390/genes14071434.Maraghechi P., Aponte M.T.S., Ecker A., et al. Pluripotency-Associated microRNAs in Early Vertebrate Embryos and Stem Cells. Genes (Basel). 2023;14(7):1434. https://doi.org/10.3390/genes14071434.Glaich O., Parikh S., Bell R.E. et al. DNA methylation directs microRNA biogenesis in mammalian cells. Nat Commun. 2019;10:5657. https://doi.org/10.1038/s41467-019-13527-1.Glaich O., Parikh S., Bell R.E. et al. DNA methylation directs microRNA biogenesis in mammalian cells. Nat Commun. 2019;10:5657. https://doi.org/10.1038/s41467-019-13527-1.Li Q., Liu J., Jia Y., Li T., Zhang M. miR-623 suppresses cell proliferation, migration and invasion through direct inhibition of XRCC5 in breast cancer. Aging (Albany NY). 2021;12:10246-10258. https://doi.org/10.18632/aging.103182.Li Q., Liu J., Jia Y., Li T., Zhang M. miR-623 suppresses cell proliferation, migration and invasion through direct inhibition of XRCC5 in breast cancer. Aging (Albany NY). 2021;12:10246 - 10258. https://doi.org/10.18632/aging.103182.Воропаева Е.И., Поспелова Т.И., Нестерец А.М., Максимов В.И. Связь микро-РНК кластера miR-143/145 с онкогенезом: тканевой и клеточный контекст. Сибирский онкологический журнал. 2023;22(3):134-143. https://doi.org/10.21294/1814-4861-2023-22-3-134-143.Voropaeva E.N., Pospelova T.I., Nesterets A.M., Maksimov V.N. Relationship between cluster miR-143/145 micro-RNAs with oncogenesis: tissue and cellular context. Siberian journal of oncology. 2023;22(3):134-143. (In Russ.) https://doi.org/10.21294/1814-4861-2023-22-3-134-143.Vallée A., Lecarpentier Y., Vallée J. N. The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions. Cancers. 2021;13(21):5557. https://doi.org/10.3390/cancers13215557.Vallée A., Lecarpentier Y., Vallée J. N. The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions. Cancers. 2021;13(21):5557. https://doi.org/10.3390/cancers13215557.Shi Z., To S., Zhang S., et al. Hypoxia-induced Nur77 activates PI3K/Akt signaling via suppression of Dicer/let-7i-5p to induce epithelial-to-mesenchymal transition. Theranostics. 2021;11:3376-3391. https://doi.org/10.7150/thno.52190.Shi Z., To S., Zhang S., et al. Hypoxia-induced Nur77 activates PI3K/Akt signaling via suppression of Dicer/let-7i-5p to induce epithelial-to-mesenchymal transition. Theranostics. 2021;11:3376 - 3391. https://doi.org/10.7150/thno.52190.Wu J., Zhu Y., Liu D., Cong Q., Bai C. Biological functions and potential mechanisms of miR-143-3p in cancers (Review). Oncology Reports. 2024;52:113. https://doi.org/10.3892/or.2024.8772.Wu J., Zhu Y., Liu D., Cong Q., Bai C. Biological functions and potential mechanisms of miR-143-3p in cancers (Review). Oncology Reports. 2024;52:113. https://doi.org/10.3892/or.2024.8772.Bautista-Sánchez D., Arriaga-Canon C., Pedroza-Torres A., et al. The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics. Mol Ther Nucleic Acids. 2020;20:409-420. https://doi.org/10.1016/j.omtn.2020.03.003.Bautista-Sánchez D., Arriaga-Canon C., Pedroza-Torres A., et al. The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics. Mol Ther Nucleic Acids. 2020;20:409-420. https://doi.org/10.1016/j.omtn.2020.03.003.Gruszka R., Zakrzewska M. The Oncogenic Relevance of miR-17-92 Cluster and Its Paralogous miR-106b-25 and miR-106a-363 Clusters in Brain Tumors. Int J Mol Sci. 2018;19(3):879. https://doi.org/10.3390/ijms19030879.Gruszka R., Zakrzewska M. The Oncogenic Relevance of miR-17-92 Cluster and Its Paralogous miR-106b-25 and miR-106a-363 Clusters in Brain Tumors. Int J Mol Sci. 2018;19(3):879. https://doi.org/10.3390/ijms19030879.Jung E., Seong Y., Jeon B., Kwon Y., Song H. MicroRNAs of miR-17-92 cluster increase gene expression by targeting mRNA-destabilization pathways.. Biochimica et biophysica acta. Gene regulatory mechanisms. 2018;1861(7): 603-612. https://doi.org/10.1016/j.bbagrm.2018.06.003.Jung E., Seong Y., Jeon B., Kwon Y., Song H. MicroRNAs of miR-17-92 cluster increase gene expression by targeting mRNA-destabilization pathways.. Biochimica et biophysica acta. Gene regulatory mechanisms. 2018;1861(7): 603-612. https://doi.org/10.1016/j.bbagrm.2018.06.003.Hossain M., Sultana A., Barua D., et al. Differential expression, function and prognostic value of miR-17-92 cluster in ER-positive and triple-negative breast cancer. Cancer treatment and research communications. 2020;25:100224 . https://doi.org/10.1016/j.ctarc.2020.100224.Hossain M., Sultana A., Barua D., et al. Differential expression, function and prognostic value of miR-17-92 cluster in ER-positive and triple-negative breast cancer.. Cancer treatment and research communications. 2020;25:100224 . https://doi.org/10.1016/j.ctarc.2020.100224.Al-Nakhle H. Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential. Current Issues in Molecular Biology. 2024;46:1832-1850. https://doi.org/10.3390/cimb46030120.Al-Nakhle H. Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential. Current Issues in Molecular Biology. 2024;46:1832 - 1850. https://doi.org/10.3390/cimb46030120.Chen X., Deng Y., Cao G., et al. Ultra-sensitive MicroRNA-21 detection based on multiple cascaded strand displacement amplification and CRISPR/Cpf1 (MC-SDA/CRISPR/Cpf1). Chemical Communications. 2021;57(52):6359–6362. https://doi.org/10.1039/d1cc01938d.Chen X., Deng Y., Cao G., et al. Ultra-sensitive MicroRNA-21 detection based on multiple cascaded strand displacement amplification and CRISPR/Cpf1 (MC-SDA/CRISPR/Cpf1). Chemical Communications. 2021;57(52):6359–6362. https://doi.org/10.1039/d1cc01938d.Liu T., Liu D., Guan S., Dong M. Diagnostic role of circulating MiR-21 in colorectal cancer: a update meta-analysis. Annals of Medicine. 2020;53:87-102. https://doi.org/10.1080/07853890.2020.1828617.Liu T., Liu D., Guan S., Dong M. Diagnostic role of circulating MiR-21 in colorectal cancer: a update meta-analysis. Annals of Medicine. 2020;53:87-102. https://doi.org/10.1080/07853890.2020.1828617.Nitusca D., Marcu A., Seclaman E. et al. Circulating microRNA-141 as a biomarker for prostate cancer: A systematic review and meta-analysis. Timisoara Med. 2022; 2022(2): 4. doi:10.35995/tmj20220204.Nitusca D., Marcu A., Seclaman E. et al. Circulating microRNA-141 as a biomarker for prostate cancer: A systematic review and meta-analysis. Timisoara Med. 2022;2022(2):4; doi:10.35995/tmj20220204.Олисова О.Ю., Амшинская Д.Р., Демкин В.В. Микро-РНК в диагностике Т-клеточных лимфом кожи. Вестник Российской академии медицинских наук. 2023;78(6):530-540.Olisova O.Y., Amshinskaya J.R., Demkin V.V. Mikro-RNK v diagnostike T-kletochnykh limfom kozhi [Micro-RNAs in the Diagnosis of Cutaneous T-Cell Lymphomas]. Vestnik Rossiyskoy akademii meditsinskikh nauk [Annals of the Russian academy of medical sciences]. 2023;78(6):530-540 (In Russ.) doi: 10.15690/vramn11612.Rhim J., Baek W., Seo Y., Kim J.H. From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer. Cells. 2022;11(18):2791. https://doi.org/10.3390/cells11182791.Rhim J., Baek W., Seo Y., Kim J.H. From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer. Cells. 2022;11(18):2791. https://doi.org/10.3390/cells11182791.Sabahi A., Salahandish R., Ghaffarinejad A., Omidinia E. Electro-chemical nano-genosensor for highly sensitive detection of miR-21 biomarker based on SWCNT-grafted dendritic Au nanostructure for early detection of prostate cancer. Talanta. 2022;209:120595 . https://doi.org/10.1016/j.talanta.2019.120595.Sabahi A., Salahandish R., Ghaffarinejad A., Omidinia E. Electro-chemical nano-genosensor for highly sensitive detection of miR-21 biomarker based on SWCNT-grafted dendritic Au nanostructure for early detection of prostate cancer.. Talanta. 2022;209:120595 . https://doi.org/10.1016/j.talanta.2019.120595.Su Y., Swiderski P., Marcucci G., Kortylewski M. Targeted Delivery of miRNA Antagonists to Myeloid Cells In Vitro and In Vivo. Methods in molecular biology. 2019;1974:141-150. https://doi.org/10.1007/978-1-4939-9220-1_10.Su Y., Swiderski P., Marcucci G., Kortylewski M. Targeted Delivery of miRNA Antagonists to Myeloid Cells In Vitro and In Vivo.. Methods in molecular biology. 2019;1974:141-150 . https://doi.org/10.1007/978-1-4939-9220-1_10.Ahir M., Upadhyay P., Ghosh A., et al. Delivery of dual miRNA through CD44-targeted mesoporous silica nanoparticles for enhanced and effective triple-negative breast cancer therapy. Biomaterials science. 2020;8:2939-2954. https://doi.org/10.1039/d0bm00015a.Ahir M., Upadhyay P., Ghosh A., et al. Delivery of dual miRNA through CD44-targeted mesoporous silica nanoparticles for enhanced and effective triple-negative breast cancer therapy. Biomaterials science. 2020;8:2939-2954. https://doi.org/10.1039/d0bm00015a.Hong D., Kang Y., Borad M., et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. British Journal of Cancer. 2020;122:1630-1637. https://doi.org/10.1038/s41416-020-0802-1.Hong D., Kang Y., Borad M., et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. British Journal of Cancer. 2020;122:1630 - 1637. https://doi.org/10.1038/s41416-020-0802-1.Capolla S., Argenziano M., Bozzer S., et al. Targeted chitosan nanobubbles as a strategy to down-regulate microRNA-17 into B-cell lymphoma models. Frontiers in immunology. 2023;14:1200310. https://doi.org/10.3389/fimmu.2023.1200310.Capolla S., Argenziano M., Bozzer S., et al. Targeted chitosan nanobubbles as a strategy to down-regulate microRNA-17 into B-cell lymphoma models. Frontiers in immunology. 2023;14:1200310. https://doi.org/10.3389/fimmu.2023.1200310.Ha J., Kim M., Lee Y., Lee M. Intranasal delivery of self-assembled nanoparticles of therapeutic peptides and antagomirs elicits anti-tumor effects in an intracranial glioblastoma model.. Nanoscale. 2021;13:14745-14759. https://doi.org/10.1039/d1nr03455c.Ha J., Kim M., Lee Y., Lee M. Intranasal delivery of self-assembled nanoparticles of therapeutic peptides and antagomirs elicits anti-tumor effects in an intracranial glioblastoma model.. Nanoscale. 2021;13:14745-14759. https://doi.org/10.1039/d1nr03455c.Mahmood M., Taufiq I., Mazhar S., et al. Revolutionizing personalized cancer treatment: the synergy of next-generation sequencing and CRISPR/Cas9. Personalized medicine. 2024;16(12):1958. https://doi.org/10.1080/17410541.2024.2341610.Mahmood M., Taufiq I., Mazhar S., et al. Revolutionizing personalized cancer treatment: the synergy of next-generation sequencing and CRISPR/Cas9. Personalized medicine. 2024;16(12):1958. https://doi.org/10.1080/17410541.2024.2341610.Wu L., Zhou W., Zhou J., et al. Circulating exosomal microRNAs as novel potential detection biomarkers in pancreatic cancer. Oncology Letters. 2020;20:1432-1440. https://doi.org/10.3892/ol.2020.11691.Wu L., Zhou W., Zhou J., et al. Circulating exosomal microRNAs as novel potential detection biomarkers in pancreatic cancer. Oncology Letters. 2020;20:1432-1440. https://doi.org/10.3892/ol.2020.11691.Rabaan A., AlSaihati H., Bukhamsin R., et al. Application of CRIS-PR/Cas9 Technology in Cancer Treatment: A Future Direction. Current Oncology. 2023;30:1954-1976. https://doi.org/10.3390/curroncol30020152.Rabaan A., AlSaihati H., Bukhamsin R., et al. Application of CRIS-PR/Cas9 Technology in Cancer Treatment: A Future Direction. Current Oncology. 2023;30:1954 - 1976. https://doi.org/10.3390/curroncol30020152.Shi S., Gu S., Han T., et al. Inhibition of MAN2A1 Enhances the Immune Response to Anti–PD-L1 in Human Tumors. Clinical Cancer Research. 2020;26:5990-6002. https://doi.org/10.1158/1078-0432.CCR-20-0778.Shi S., Gu S., Han T., et al. Inhibition of MAN2A1 Enhances the Immune Response to Anti–PD-L1 in Human Tumors. Clinical Cancer Research. 2020;26:5990 - 6002. https://doi.org/10.1158/1078-0432.CCR-20-0778.

The authors declare that there are no conflicts of interest present.