m6A甲基转移酶KIAA1429人类疾病的作用 机制研究进展
Research Progress on the Mechanistic Roles of m6A Methyltransferase KIAA1429 in Human Diseases
DOI: 10.12677/acm.2026.1641643, PDF,    科研立项经费支持
作者: 耿肖玉捷, 刘 洋*：昆明医科大学第二附属医院生殖医学科，云南 昆明
关键词: KIAA1429；m6A修饰；机制；治疗靶点；KIAA1429； m6A Modification； Mechanism； Therapeutic Target
摘要: 病毒样甲基转移酶相关蛋白(vir-like m6A methyltransferase associated, also known by VIRMA)是N6-腺苷酸甲基化(N6-methyladenosine, m6A)转移酶复合物中重要组成部分，又被称为KIAA1429，是m6A修饰中关键的病毒样甲基化转移酶，主要是通过调控m6A修饰水平，影响RNA的稳定性、剪接、翻译等多个方面，进而参与多种疾病的发生和发展。本文重点探讨KIAA1429在癌症中的致瘤作用以及在相关非肿瘤性疾病中的潜在影响，旨在揭示KIAA1429在疾病发展中的作用机制。
Abstract: Vir-like m6A methyltransferase associated protein (VIRMA), also known as KIAA1429, is a crucial component of the N6-methyladenosine (m6A) methyltransferase complex and serves as a key vir-like methyltransferase in m6A modification. It primarily regulates m6A modification levels, thereby influencing RNA stability, splicing, translation, and other processes, consequently participating in the occurrence and progression of various diseases. This article focuses on the oncogenic role of KIAA1429 in cancers and its potential implications in related non-neoplastic diseases, aiming to elucidate the mechanistic roles of KIAA1429 in disease development.
文章引用：耿肖玉捷, 刘洋. m6A甲基转移酶KIAA1429人类疾病的作用 机制研究进展[J]. 临床医学进展, 2026, 16(4): 3764-3771. https://doi.org/10.12677/acm.2026.1641643

参考文献

[1] Wang, W., Liu, H., Liu, S., Hao, T., Wei, Y., Wei, H., et al. (2024) Oocyte-Specific Deletion of Eukaryotic Translation Initiation Factor 5 Causes Apoptosis of Mouse Oocytes within the Early-Growing Follicles by Mitochondrial Fission Defect-Reactive Oxygen Species-DNA Damage. Clinical and Translational Medicine, 14, e1791. [Google Scholar] [CrossRef] [PubMed]
[2] Fu, Y., Dominissini, D., Rechavi, G. and He, C. (2014) Gene Expression Regulation Mediated through Reversible m6A RNA Methylation. Nature Reviews Genetics, 15, 293-306. [Google Scholar] [CrossRef] [PubMed]
[3] Deng, X., Chen, K., Luo, G.Z., et al. (2015) Widespread Occurrence of N6-Methyladenosine in Bacterial mRNA. Nucleic Acids Research, 43, 6557-6567.
[4] Qin, Y., Li, L., Luo, E., Hou, J., Yan, G., Wang, D., et al. (2020) Role of m6A RNA Methylation in Cardiovascular Disease (Review). International Journal of Molecular Medicine, 46, 1958-1972. [Google Scholar] [CrossRef] [PubMed]
[5] Huang, H., Weng, H., Sun, W., Qin, X., Shi, H., Wu, H., et al. (2018) Recognition of RNA N6-Methyladenosine by IGF2BP Proteins Enhances mRNA Stability and Translation. Nature Cell Biology, 20, 285-295. [Google Scholar] [CrossRef] [PubMed]
[6] Ma, S., Chen, C., Ji, X., Liu, J., Zhou, Q., Wang, G., et al. (2019) The Interplay between m6A RNA Methylation and Noncoding RNA in Cancer. Journal of Hematology & Oncology, 12, Article No. 121. [Google Scholar] [CrossRef] [PubMed]
[7] Zhang, Y., Geng, X., Li, Q., Xu, J., Tan, Y., Xiao, M., et al. (2020) m6A Modification in RNA: Biogenesis, Functions and Roles in Gliomas. Journal of Experimental & Clinical Cancer Research, 39, Article No. 192. [Google Scholar] [CrossRef] [PubMed]
[8] Lan, T., Li, H., Zhang, D., Xu, L., Liu, H., Hao, X., et al. (2019) KIAA1429 Contributes to Liver Cancer Progression through N6-Methyladenosine-Dependent Post-Transcriptional Modification of GATA3. Molecular Cancer, 18, Article No. 186. [Google Scholar] [CrossRef] [PubMed]
[9] Zhu, B., Chen, H., Li, S., Tan, J., Xie, Y., Zou, M., et al. (2021) Comprehensive Analysis of N6-Methyladenosine (m6A) Modification during the Degeneration of Lumbar Intervertebral Disc in Mice. Journal of Orthopaedic Translation, 31, 126-138. [Google Scholar] [CrossRef] [PubMed]
[10] Schwartz, S., Mumbach, M.R., Jovanovic, M., Wang, T., Maciag, K., Bushkin, G.G., et al. (2014) Perturbation of m6A Writers Reveals Two Distinct Classes of mRNA Methylation at Internal and 5’ Sites. Cell Reports, 8, 284-296. [Google Scholar] [CrossRef] [PubMed]
[11] Han, D., Longhini, A.P., Zhang, X., Hoang, V., Wilson, M.Z. and Kosik, K.S. (2022) Dynamic Assembly of the mRNA m6A Methyltransferase Complex Is Regulated by METTL3 Phase Separation. PLOS Biology, 20, e3001535. [Google Scholar] [CrossRef] [PubMed]
[12] Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. [Google Scholar] [CrossRef] [PubMed]
[13] Yang, Y., Gao, F., Ren, L., Ren, N., Pan, J. and Xu, Q. (2024) Functions and Mechanisms of RNA m6A Regulators in Breast Cancer (Review). International Journal of Oncology, 65, Article No. 86. [Google Scholar] [CrossRef] [PubMed]
[14] Qian, J.Y., Gao, J., Sun, X., et al. (2019) KIAA1429 Acts as an Oncogenic Factor in Breast Cancer by Regulating CDK1 in an N6-Methyladenosine-Independent Manner. Oncogene, 38, 6123-6141. [Google Scholar] [CrossRef] [PubMed]
[15] Zhang, X., Dai, X.Y., Qian, J.Y., et al. (2022) SMC1A Regulated by KIAA1429 in m6A-Independent Manner Promotes EMT Progress in Breast Cancer. Molecular Therapy Nucleic Acids, 27, 133-146. [Google Scholar] [CrossRef] [PubMed]
[16] Kuang, Y., Cheng, Y., Wang, J., Li, H., Cao, X. and Wang, Y. (2022) KIAA1429 Mediates Epithelial Mesenchymal Transition in Sorafenib-Resistant Hepatocellular Carcinoma through m6A Methylation Modification. Cancer Medicine, 12, 7222-7233. [Google Scholar] [CrossRef] [PubMed]
[17] Ren, S., Zhang, Y., Yang, X., Li, X., Zheng, Y., Liu, Y., et al. (2022) N6-Methyladenine-Induced LINC00667 Promoted Breast Cancer Progression through m6A/KIAA1429 Positive Feedback Loop. Bioengineered, 13, 13462-13473. [Google Scholar] [CrossRef] [PubMed]
[18] 李照, 朱继业. 《原发性肝癌诊疗指南(2024年版)》解读[J]. 临床肝胆病杂志, 2024, 40(7): 1324-1327.
[19] Gao, R., Ye, M., Liu, B., Wei, M., Ma, D. and Dong, K. (2021) m6A Modification: A Double-Edged Sword in Tumor Development. Frontiers in Oncology, 11, Article 679367. [Google Scholar] [CrossRef] [PubMed]
[20] Cheng, X., Li, M., Rao, X., et al. (2019) KIAA1429 Regulates the Migration and Invasion of Hepatocellular Carcinoma by Altering m6A Modification of ID2 mRNA. OncoTargets and Therapy, 12, 3421-3428. [Google Scholar] [CrossRef] [PubMed]
[21] Wang, M., Yang, Y., Yang, J., Yang, J. and Han, S. (2020) Circ_KIAA1429 Accelerates Hepatocellular Carcinoma Advancement through the Mechanism of m6A-YTHDF3-Zeb1. Life Sciences, 257, Article 118082. [Google Scholar] [CrossRef] [PubMed]
[22] Wang, H., Chen, W., Cui, Y., Gong, H. and Li, H. (2023) KIAA1429 Protects Hepatocellular Carcinoma Cells from Ferroptotic Cell Death with a m6A-Dependent Posttranscriptional Modification of SLC7A11. Journal of Cellular and Molecular Medicine, 27, 4118-4132. [Google Scholar] [CrossRef] [PubMed]
[23] Biller, L.H. and Schrag, D. (2021) Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. Journal of the American Medical Association, 325, 669-685. [Google Scholar] [CrossRef] [PubMed]
[24] 刘萌萌, 李付广. MAD2L1在结直肠癌中的表达及与免疫浸润关系的研究[J]. 临床研究, 2024, 32(5): 5-9.
[25] Zhou, Y., Pei, Z., Maimaiti, A., Zheng, L., Zhu, Z., Tian, M., et al. (2022) m6A Methyltransferase KIAA1429 Acts as an Oncogenic Factor in Colorectal Cancer by Regulating SIRT1 in an m6A-Dependent Manner. Cell Death Discovery, 8, Article No. 83. [Google Scholar] [CrossRef] [PubMed]
[26] 叶春水. Kiaa1429通过调控细胞凋亡促进结肠癌细胞恶性进展的机制研究[D]: [硕士学位论文]. 济南: 山东大学, 2024.
[27] Chen, X., Sun, K., Jiao, S., Cai, N., Zhao, X., Zou, H., et al. (2014) High Levels of SIRT1 Expression Enhance Tumorigenesis and Associate with a Poor Prognosis of Colorectal Carcinoma Patients. Scientific Reports, 4, Article No. 7481. [Google Scholar] [CrossRef] [PubMed]
[28] Miao, R., Dai, C.C., Mei, L., et al. (2020) KIAA1429 Regulates Cell Proliferation by Targeting c‐Jun Messenger RNA Directly in Gastric Cancer. Journal of Cellular Physiology, 235, 7420-7432. [Google Scholar] [CrossRef] [PubMed]
[29] Yang, D., Chang, S., Li, F., Ma, M., Yang, J., Lv, X., et al. (2021) m6A Transferase KIAA1429-Stabilized LINC00958 Accelerates Gastric Cancer Aerobic Glycolysis through Targeting GLUT1. IUBMB Life, 73, 1325-1333. [Google Scholar] [CrossRef] [PubMed]
[30] Zhao, W. and Xie, Y. (2021) KIAA1429 Promotes the Progression of Lung Adenocarcinoma by Regulating the m6A Level of MUC3A. Pathology—Research and Practice, 217, Article 153284. [Google Scholar] [CrossRef] [PubMed]
[31] Zhang, C., Sun, Q., Zhang, X., Qin, N., Pu, Z., Gu, Y., et al. (2022) Gene Amplification-Driven RNA Methyltransferase KIAA1429 Promotes Tumorigenesis by Regulating BTG2 via m6A-YTHDF2-Dependent in Lung Adenocarcinoma. Cancer Communications, 42, 609-626. [Google Scholar] [CrossRef] [PubMed]
[32] Tang, J., Han, T., Tong, W., Zhao, J. and Wang, W. (2021) N6-Methyladenosine (m6A) Methyltransferase KIAA1429 Accelerates the Gefitinib Resistance of Non-Small-Cell Lung Cancer. Cell Death Discovery, 7, Article No. 108. [Google Scholar] [CrossRef] [PubMed]
[33] Gan, L., Zhao, S., Gao, Y., Qi, Y., Su, M., Wang, A., et al. (2023) N6-Methyladenosine Methyltransferase KIAA1429 Promoted Ovarian Cancer Aerobic Glycolysis and Progression through Enhancing ENO1 Expression. Biology Direct, 18, Article No. 64. [Google Scholar] [CrossRef] [PubMed]
[34] Fan, L., Lin, Y., Lei, H., Shu, G., He, L., Yan, Z., et al. (2020) A Newly Defined Risk Signature, Consisting of Three M6a RNA Methylation Regulators, Predicts the Prognosis of Ovarian Cancer. Aging, 12, 18453-18475. [Google Scholar] [CrossRef] [PubMed]
[35] Walsh, T.J., Grady, R.W., Porter, M.P., Lin, D.W. and Weiss, N.S. (2006) Incidence of Testicular Germ Cell Cancers in U.S. Children: SEER Program Experience 1973 to 2000. Urology, 68, 402-405. [Google Scholar] [CrossRef] [PubMed]
[36] Chia, V.M., Quraishi, S.M., Devesa, S.S., Purdue, M.P., Cook, M.B. and McGlynn, K.A. (2010) International Trends in the Incidence of Testicular Cancer, 1973-2002. Cancer Epidemiology, Biomarkers & Prevention, 19, 1151-1159. [Google Scholar] [CrossRef] [PubMed]
[37] Nettersheim, D., Berger, D., Jostes, S., Kristiansen, G., Lochnit, G. and Schorle, H. (2019) N6-Methyladenosine Detected in RNA of Testicular Germ Cell Tumors Is Controlled by METTL3, ALKBH5, YTHDC1/F1/F2, and HNRNPC as Writers, Erasers, and Readers. Andrology, 7, 498-506. [Google Scholar] [CrossRef] [PubMed]
[38] Miranda-Gonçalves, V., Lobo, J., Guimarães-Teixeira, C., Barros-Silva, D., Guimarães, R., Cantante, M., et al. (2021) The Component of the m6A Writer Complex VIRMA Is Implicated in Aggressive Tumor Phenotype, DNA Damage Response and Cisplatin Resistance in Germ Cell Tumors. Journal of Experimental & Clinical Cancer Research, 40, Article No. 268. [Google Scholar] [CrossRef] [PubMed]
[39] Qiu, S., Li, W., Xiong, H., Liu, D., Bai, Y., Wu, K., et al. (2016) Single-Cell RNA Sequencing Reveals Dynamic Changes in A-to-I RNA Editome during Early Human Embryogenesis. BMC Genomics, 17, Article No. 766. [Google Scholar] [CrossRef] [PubMed]
[40] Hu, Y., Ouyang, Z., Sui, X., Qi, M., Li, M., He, Y., et al. (2020) Oocyte Competence Is Maintained by m6A Methyltransferase KIAA1429-Mediated RNA Metabolism during Mouse Follicular Development. Cell Death & Differentiation, 27, 2468-2483. [Google Scholar] [CrossRef] [PubMed]
[41] 杨娜, 刘静. 动脉粥样硬化性心血管病的预防[J]. 中华心血管病杂志, 2022, 50(3): 309-313.
[42] Wang, P., Wang, Z., Zhang, M., Wu, Q., Shi, F. and Yuan, S. (2021) KIAA1429 and ALKBH5 Oppositely Influence Aortic Dissection Progression via Regulating the Maturation of pri-miR-143-3p in an m6A-Dependent Manner. Frontiers in Cell and Developmental Biology, 9, Article 668377. [Google Scholar] [CrossRef] [PubMed]

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