设为首页 加入收藏 期刊导航 网站地图

Advances in Clinical Medicine
Vol. 13  No. 03 ( 2023 ), Article ID: 62754 , 6 pages
10.12677/ACM.2023.133556

m6A与LncRNA之间在胰腺癌中的应用及展望

朱刚霞，张莉*

新疆医科大学第一附属医院综合内四科，新疆 乌鲁木齐

收稿日期：2023年2月15日；录用日期：2023年3月11日；发布日期：2023年3月20日

摘要

胰腺癌是消化道肿瘤中具有侵袭性和致命性的恶性肿瘤，预后差。m6A是最常见转录后修饰，在RNA的输出、翻译、稳定、成熟和衰变起着至关重要的作用。LncRNA是一类转录长度超过200nt的分子，通常情况下不直接参与蛋白质编码过程，而是以RNA的形式参与蛋白质编码基因的调控。对于m6A修饰与lncRNA之间的相关研究也正在进行中。本文围绕m6A与lncRNA在PAAD中的最新研究及进展作一综述。

关键词

n6-甲基腺苷(m6A)，长链非编码RNA，胰腺癌

Application and Prospect between m6A and LncRNA in Pancreatic Cancer

Gangxia Zhu, Li Zhang*

Department of Comprehensive Internal Medicine IV, The First Affiliated Hospital of Xinjiang Medical University, Urumqi Xinjiang

Received: Feb. 15th, 2023; accepted: Mar. 11th, 2023; published: Mar. 20th, 2023

ABSTRACT

Pancreatic cancer is an aggressive and lethal malignancy among GI tract tumors with poor prognosis. m6A is the most common post-transcriptional modification and plays a crucial role in RNA output, translation, stabilization, maturation and decay. lncRNA is a class of molecules with transcriptional length over 200 nt, which normally do not participate in protein coding process directly, but in the form of RNA in protein coding gene regulation. Studies on the correlation between m6A modifications and lncRNAs are also underway. This paper presents a review of the latest research progress between m6A and lncRNA in PAAD, aiming to discuss the latest research and progress between m6A and LncRNA in pancreatic cancer.

Keywords:n6-Methyladenosine (m6A), Long-Stranded Non-Coding RNA, Pancreatic Cancer

Copyright © 2023 by author(s) and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

http://creativecommons.org/licenses/by/4.0/

1. 引言

胰腺癌(Pancreatic Cancer, PC)是一种非常常见消化道肿瘤，也是最有侵袭性和致命性的恶性肿瘤之一。在所有的人类原发癌症中，预后差。根据美国癌症协会的数据，2019年约有5.6万例胰腺癌新发病例，死亡人数估计有4.5万人，是全球男性和女性癌症死亡的第七大原因 [1]。目前，胰腺癌的具体发病原因仍未完全阐明，但有研究显示与遗传、生活和饮食习惯及慢性损伤等因素均有关 [2]，例如吸烟、喝酒、慢性胰腺炎及家族遗传史等。手术是目前唯一可能治愈手段并使5年生存率提高到20%~30%的方法。不幸的是，通常由于缺乏特异性的症状，发现时多已出现扩散及转移，使手术切除困难 [3]。虽然目前有不同的治疗方法，如新辅助治疗、化疗、放疗、靶向治疗及免疫治疗，但其临床效果并不理想 [3]。对于PC患者，如果能够早期诊断并接受治疗可大大提高患者生存率。大多数化疗患者已经有局部晚期或转移性病灶。因此，在胰腺癌的早期诊断、预后判断、治疗策略选择等方面，具有灵敏、准确的分子标志物是十分必要的。越来越多的证据表明，RNA修饰途径在人类癌症中是存在错误调控，可能是癌症治疗的理想靶点 [4]。目前已有超过100不同类型的合成后修饰被证明存在于RNA上，包括mRNA、microRNA和长链非编码RNA (lncRNA) [4]，在这些修饰中，甲基化修饰最为丰富，包括n6-甲基腺苷(m6A)、5-甲基胞嘧啶(m5C)、n1-甲基腺苷(m1A) [5] [6]，其中，m6A是最常见转录后修饰，在RNA的输出、翻译、稳定、成熟和衰变起着至关重要的作用 [7] [8]。m6A的调节因子分为3种类型：甲基转移酶(Writer)、去甲基化酶(Erasers)和信号转导器(Reader) [9]，可以潜在地诱导m6A积极参与膀胱癌 [10] 、胃癌 [11] 和胰腺癌 [12] 等多种肿瘤的发生和发展。m5C是人类另一种丰富的RNA修饰，首次在稳定且高度丰富的tRNAs和rRNAs中被发现 [13]。m5C甲基化修饰是一个可逆的过程，包括甲基转移酶(Writer)、去甲基化酶(Erasers)和结合蛋白(Reader)等相关酶动态调节 [14]。有研究表明在几种癌症中m5C异常表达在发挥致癌作用，包括胰腺癌 [15] 、胃癌 [16] 、膀胱癌 [17] 等。长链非编码RNA (Long non-coding, lncRNA)是一种核糖核苷酸链，长度为200个核苷酸 [18]。lncRNA以前被认为缺乏任何生物学功能，因为它们不具有蛋白质编码能力。然而，研究发现lncRNA可以通过转录水平的表观遗传调控 [19] 、转录后水平的表观遗传调控 [20] 或组蛋白修饰 [21] 来发挥其生物学功能。有研究揭示了lncRNA参与了各种生物过程的调节，包括肿瘤发生和肿瘤免疫 [22]。

2. m6A概述

m6A修饰是一个动态和可逆的过程，在调节RNA稳定性、剪接和翻译方面具有关键作用。这种修饰由被称为m6A甲基转移酶复合物(写入器)、m6A去甲基酶(擦除器)和m6A结合蛋白(读取器) [9]。

2.1. m6A甲基转移酶

m6A甲基转移酶被称为“写入器”，包括甲基转移酶样3/14/16 (METTL3/14/16)、wt1相关蛋白(WTAP)、RNA结合图案蛋白15/15B (RBM15/15B)和病毒样m6A甲基转移酶相关蛋白(VIRMA，也称为KIAA1429) [23]。METTL3/14可以形成复合物，使m6A甲基化写入mRNA，18而WTAP帮助METTL3/14定位核点，并在体内维持m6A甲基转移酶的催化活性。同时，METTL3的表达对WTAP蛋白的稳态至关重要 [24]。

2.2. m6A去甲基酶

m6A甲基化是动态的，可以被m6A去甲基化酶(也被称为m6A“擦除器”)逆转，包括FTO和AlkB同源物5 (ALKBH5) [25] [26]。它们都属于AlkB亚家族。FTO和AlkBH5使用铁亚铁作为辅因子，α-酮戊二酸作为辅底物催化底物的氧化 [26]。这些蛋白可以通过一系列复杂的中间反应选择性地去除针对mRNA的m6A标记，从而影响肿瘤特定的生物过程。

2.3. m6A结合蛋白

m6A结合蛋白子被称为“读取器”，最常见的包括m6A RNA结合蛋白1/2/3 (YTHDF1/2/3)，含YTH结构域的1/2 (YTHDC1/2)，胰岛素样生长因子2 mRNA结合蛋白1/2/3 (IGF2BP1/2/3)，异质核核糖核蛋白(HNRNPs)和含锌指CCCH结构域的蛋白13 (ZC3H13) [27]。

经典m6A调控因子中，METTL3、METTL14、WTAP、FTO、YTHDF2、IGF2BP1-3、hnRNPC、NKAP在胰腺癌中表达上调，METTL16、ALKBH5在胰腺癌中表达下调 [28]。m6A修饰已被研究用于胰腺癌治疗。m6A及其相关因子在胰腺癌细胞和患者中表达异常，在胰腺癌诊断和靶向治疗中具有潜在的新型生物标志物价值。研究表明，m6A修饰可调节胰腺癌的肿瘤发生和进展。例如，m6A甲基转移酶METTL3促进胰腺癌细胞增殖、侵袭、化疗耐药和放射耐药 [29] [30]。m6A去甲基酶HNRNPC的上调与rs7495G有关，它通过miRNA介导的方式赋予胰腺癌较高的风险 [31]。m6A结合蛋白ALKBH5通过m6A的取消，通过PER1的转录后激活，降低wwi-1 RNA甲基化和介导Wnt信号，防止胰腺癌进展 [32] [33]。

3. 胰腺癌中lncRNAs的m6A修饰

lncRNA是长度超过200个核苷酸的非编码RNA亚群，在癌症中可以被m6A甲基化修饰。根据lncRNA的功能，可将其分为信号lncRNA、诱饵lncRNA、引导lncRNA和支架lncRNA。lncRNA的异常表达会破坏生物体内的稳态，并可能驱动或抑制各种癌症 [34]，同时与肿瘤恶性程度密切相关。m6A甲基化促进了lncRNA X-非活性特定转录物(X-Inactive Specific Transcripts, XIST)介导的转录抑制 [35] [36] [37]。YTHDC1优先识别XIST和RBM15/15B的m6A残基，参与XIST介导的 [37] 基因沉默。然而，据报道，RBM15/m6A-MTase复合物在XIST介导的 [38] 基因沉默中起次要作用。YTHDF2识别lnc-Dpf3的m6A甲基化位点，促进其降解，并增强lnc-Dpf3与缺氧诱导因子1-α (HIF-1α)的结合，从而抑制树突状细胞的糖酵解和迁移 [39]。研究表明，m6A修饰通过m6A去甲基化酶依赖的方式调控癌细胞增殖，特异的m6A读取器YTHDF1和YTHDF2能够读取m6A基序，调控lncRNA THOR的稳定性(稳定和衰退) [40]。He Y等人还发现m6A擦除ALKBH5在肿瘤组织中表达下调，可以使KCNK15-AS1脱甲基，并调节KCNK15-AS1的表达。ALKBH5还参与KCNK15-AS1介导的细胞迁移和侵袭 [12]。在未来，ALKBH5-KCNK15-AS1有可能作为胰腺癌患者的治疗靶点。在细胞核中，lncRNA可能会招募调节蛋白并与mRNA相互作用，或作为竞争性的内源性RNA (ceRNA)，调节mRNA的翻译和稳定性 [41]。因此，我们推断m6A修饰可能会影响细胞质lncRNA的类似调节功能。然而，我们对lncRNA的m6A修饰的理解仍然是有限的。有研究利用生物信息学筛选m6a相关lncRNA构建预后相关模型，MEG9、AC092171.5和AC002091.1在低危患者中高表达，这三种lncrna可能抑制胰腺腺癌的发生 [42]，为进一步探索基于m6a相关lncRNAs诊断和治疗胰腺癌的生物标志物和免疫机制提供了基础。到目前为止，只有少数研究提出m6A调控因子可以通过修饰特定的lncRNA来维持胰腺癌的恶性。例如，Hu等人证明lncRNA DANCR通过m6A修饰靶向IGF2BP2，IGF2BP2和DANCR共同促进癌干样特性和胰腺癌发病机制 [43]。孟等人发现m6A在LINC00857中高度富集，并增强了其RNA稳定性。同时，LINC00857通过与miR-150-5p结合来调节E2F3的表达，最终促进胰腺癌的肿瘤发生 [12]。基于以上研究，我们认为lncRNA参与了m6A修饰，应该更加关注lncRNA与m6A修饰的相互作用和功能，以确定胰腺癌的预后标志物和治疗靶点。

4. 小结及展望

PC是一种异质性、高度恶性的肿瘤，其发病率和死亡率高 [44]。对于胰腺癌患者所面临的问题是早期诊断、准确预测肿瘤进展和有效干预。目前建立PC治疗反应和预后的临床标志物大多基于临床特征，其准确性和特异性有限。越来越多的研究证实了lncRNA中几种常见修饰(m6A、m5C及m1A)参与肿瘤的进展 [7]，包括促进癌细胞增殖或调节侵袭性和转移潜能 [4]。m6A可以参与肿瘤增殖、迁移、耐药或作为肿瘤预后标志物 [45]。例如，m6A去甲基酶 YTHDF2介导lncRNA FENDRR降解子宫内膜样癌(EEC)中促进细胞增殖 [46]。相反，m6A介导LNCAROD过表达通过促进YBX1 HSPA1A相互作用促进HNSCC恶性发展 [47]。以上表明，RNA甲基化修饰语lncRNAs在多种肿瘤发生过程中存在相关作用。目前，RNA甲基化和翻译组学是表观遗传学研究的新方向，将为研究正常生理和异常细胞过程的新机制提供重要的见解。非编码RNA与m6A修饰的功能相互作用研究尤其值得关注。研究非编码RNA与m6A修饰的交叉调控，将有助于发现胰腺癌癌症患者诊断和治疗的关键靶点，这是个性化医疗的最终目标。以往的研究已经证实了m6A修饰与lncRNAs在各种生理病理过程中的重要作用，因此m6A修饰与lncRNAs越来越受到重视。更多的研究集中在m6A修饰与lncRNAs的机制上，并确定了越来越多的相关因子。因此，我们需要更多的研究来阐明m6A修饰如何选择性地识别和结合特定的RNA，以及m6A修饰是发挥竞争作用还是协同作用。此外，特定的m6A相关因子在各种癌症中的作用也各不相同。虽然许多研究证实了m6A与PC的发展密切相关，但我们对m6A在PC中的作用的认识还远远不够。进一步的研究需要集中于通过m6A修饰和m6A相关因子抑制剂的临床应用来确定早期诊断PC的策略。

文章引用

朱刚霞,张 莉. m6A与LncRNA之间在胰腺癌中的应用及展望
Application and Prospect between m6A and LncRNA in Pancreatic Cancer[J]. 临床医学进展, 2023, 13(03): 3883-3888. https://doi.org/10.12677/ACM.2023.133556

参考文献

  1. 1. Ferlay, J., Soerjomataram, I., Dikshit, R., et al. (2015) Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012. International Journal of Cancer, 136, E359-E386. https://doi.org/10.1002/ijc.29210

  2. 2. Zhao, Z. and Liu, W. (2020) Pancreatic Cancer: A Review of Risk Factors, Diagnosis, and Treatment. Technology in Cancer Research & Treatment, 19. https://doi.org/10.1177/1533033820962117

  3. 3. Mizrahi, J.D., Surana, R., Valle, J.W. and Shroff, R.T. (2020) Pancreatic Cancer. The Lancet, 395, 2008-2020. https://doi.org/10.1016/S0140-6736(20)30974-0

  4. 4. Barbieri, I. and Kouzarides, T. (2020) Role of RNA Modi-fications in Cancer. Nature Reviews Cancer, 20, 303-322. https://doi.org/10.1038/s41568-020-0253-2

  5. 5. Zhao, B.S., Roundtree, I.A. and He, C. (2017) Post-Transcriptional Gene Regulation by mRNA Modifications. Nature Reviews Molecular Cell Biology, 18, 31-42. https://doi.org/10.1038/nrm.2016.132

  6. 6. Yi, Y.C., Chen, X.Y., Zhang, J. and Zhu, J.S. (2020) Novel Insights into the Interplay between m6A Modification and Noncoding RNAs in Cancer. Molecular Cancer, 19, Article No. 121. https://doi.org/10.1186/s12943-020-01233-2

  7. 7. Wang, S., Sun, C., Li, J., et al. (2017) Roles of RNA Meth-ylation by Means of N6-Methyladenosine (m6A) in Human Cancers. Cancer Letters, 408, 112-120. https://doi.org/10.1016/j.canlet.2017.08.030

  8. 8. Du, K., Zhang, L., Lee, T. and Sun, T. (2019) m6A RNA Methylation Controls Neural Development and Is Involved in Human Diseases. Molecular Neurobiology, 56, 1596-1606. https://doi.org/10.1007/s12035-018-1138-1

  9. 9. He, L., Li, H., Wu, A., Peng, Y., Shu, G. and Yin, G. (2019) Functions of N6-Methyladenosine and Its Role in Cancer. Molecular Cancer, 18, Article No. 176. https://doi.org/10.1186/s12943-019-1109-9

  10. 10. Han, J., Wang, J.Z., Yang, X., et al. (2019) METTL3 Promote Tumor Proliferation of Bladder Cancer by Accelerating pri-miR221/222 Maturation in m6A-Dependent Manner. Mo-lecular Cancer, 18, Article No. 110. https://doi.org/10.1186/s12943-019-1036-9

  11. 11. Wang, Q., Chen, C., Ding, Q., et al. (2020) METTL3-Mediated m6A Modification of HDGF mRNA Promotes Gastric Cancer Progression and Has Prognostic Significance. Gut, 69, 1193-1205. https://doi.org/10.1136/gutjnl-2019-319639

  12. 12. He, Y., Hu, H., Wang, Y., et al. (2018) ALKBH5 Inhibits Pan-creatic Cancer Motility by Decreasing Long Non-Coding RNA KCNK15-AS1 Methylation. Cellular Physiology and Biochemistry, 48, 838-846. https://doi.org/10.1159/000491915

  13. 13. Yang, X., Yang, Y., Sun, B.F., et al. (2017) 5-Methylcytosine Promotes mRNA Export—NSUN2 as the methyltransferase and ALYREF as an m5C Reader. Cell Research, 27, 606-625. https://doi.org/10.1038/cr.2017.55

  14. 14. Cabrita, R., Lauss, M., Sanna, A., et al. (2020) Tertiary lymphoid Struc-tures Improve Immunotherapy and Survival in Melanoma. Nature, 577, 561-565. https://doi.org/10.1038/s41586-019-1914-8

  15. 15. Havel, J.J., Chowell, D. and Chan, T.A. (2019) The Evolving Landscape of Biomarkers for Checkpoint Inhibitor Immunotherapy. Nature Reviews Cancer, 19, 133-150. https://doi.org/10.1038/s41568-019-0116-x

  16. 16. Petitprez, F., de Reyniès, A., Keung, E.Z., et al. (2020) B Cells Are Associated with Survival and Immunotherapy Response in Sarcoma. Nature, 577, 556-560. https://doi.org/10.1038/s41586-019-1906-8

  17. 17. Darvin, P., Toor, S.M., Nair, S.V. and Elkord, E. (2018) Immune Checkpoint Inhibitors: Recent Progress and Potential Biomarkers. Experimental & Molecular Medicine, 50, 1-11. https://doi.org/10.1038/s12276-018-0191-1

  18. 18. Kopp, F. and Mendell, J.T. (2018) Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell, 172, 393-407. https://doi.org/10.1016/j.cell.2018.01.011

  19. 19. Wei, J.W., Huang, K., Yang, C. and Kang, C.S. (2017) Non-Coding RNAs as Regulators in Epigenetics (Review) Oncology Reports, 37, 3-9. https://doi.org/10.3892/or.2016.5236

  20. 20. Dykes, I.M. and Emanueli, C. (2017) Transcriptional and Post-Transcriptional Gene Regulation by Long Non-Coding RNA. Genomics, Proteomics & Bioinformatics, 15, 177-186. https://doi.org/10.1016/j.gpb.2016.12.005

  21. 21. Tsai, M.C., Manor, O., Wan, Y., Mosammaparast, N., Wang, J.K., Lan, F., Shi, Y., Segal, E. and Chang, H.Y. (2010) Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes. Science, 329, 689-693. https://doi.org/10.1126/science.1192002

  22. 22. Dai, F., Wu, Y., Lu, Y., et al. (2020) Crosstalk between RNA m6A Modification and Non-Coding RNA Contributes to Cancer Growth and Progression. Molecular Therapy Nucleic Acids, 22, 62-71. https://doi.org/10.1016/j.omtn.2020.08.004

  23. 23. Ping, X.L., Sun, B.F., Wang, L., et al. (2014) Mammalian WTAP Is a Regulatory Subunit of the RNA N6-Methyladenosine Methyltransferase. Cell Research, 24, 177-189. https://doi.org/10.1038/cr.2014.3

  24. 24. Sorci, M., Ianniello, Z., Cruciani, S., et al. (2018) METTL3 Regulates WTAP Protein Homeostasis. Cell Death & Disease, 9, Article No. 796. https://doi.org/10.1038/s41419-018-0843-z

  25. 25. Zheng, G., Dahl, J.A., Niu, Y., et al. (2013) ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility. Mol Cell, 49, 18-29. https://doi.org/10.1016/j.molcel.2012.10.015

  26. 26. Jia, G., Fu, Y., Zhao, X., et al. (2011) N6-Methyladenosine in Nuclear RNA Is a Major Substrate of the Obesity-Associated FTO. Nature Chemical Biology, 7, 885-887. https://doi.org/10.1038/nchembio.687

  27. 27. Meyer, K.D. and Jaffrey, S.R. (2017) Rethinking m6A Readers, Writers, and Erasers. Annual Review of Cell and Developmental Biology, 33, 319-342. https://doi.org/10.1146/annurev-cellbio-100616-060758

  28. 28. Chen, S., Ren, H., Zhang, X., et al. (2022) Research Advances of N6-Methyladenosine in Diagnosis and Therapy of Pancreatic Cancer. Journal of Clinical Laboratory Analysis, 36, e24611. https://doi.org/10.1002/jcla.24611

  29. 29. Xia, T., Wu, X., Cao, M., Zhang, P., Shi, G., Zhang, J., et al. (2019) The RNA m6A Methyltransferase METTL3 Promotes Pancreatic Cancer Cell Proliferation and Invasion. Pathology-Research and Practice, 215, Article ID: 152666. https://doi.org/10.1016/j.prp.2019.152666

  30. 30. Taketo, K., Konno, M., Asai, A., Koseki, J., Toratani, M., Satoh, T., et al. (2018) The Epitranscriptome m6A Writer METTL3 Promotes Chemo- and Radioresistance in Pancreatic Cancer Cells. International Journal of Oncology, 52, 621-9. https://doi.org/10.3892/ijo.2017.4219

  31. 31. Ying, P., Li, Y., Yang, N., Wang, X., Wang, H., He, H., et al. (2021) Identification of Genetic Variants in m6A Modification Genes Associated with Pancreatic Cancer Risk in the Chinese Population. Archives of Toxicology, 95, 1117-1128. https://doi.org/10.1007/s00204-021-02978-5

  32. 32. Guo, X., Li, K., Jiang, W., Hu, Y., Xiao, W., Huang, Y., et al. (2020) RNA Demethylase ALKBH5 Prevents Pancreatic Cancer Progression by Posttranscriptional Activation of PER1 in an m6A-YTHDF2-Dependent Manner. Molecular Cancer, 19, Article No. 91. https://doi.org/10.1186/s12943-020-01158-w

  33. 33. Tang, B., Yang, Y., Kang, M., Wang, Y.S., Wang, Y., Bi, Y., et al. (2020) m6A Demethylase ALKBH5 Inhibits Pancreatic Cancer Tumorigenesis by Decreasing WIF-1 RNA Methylation and Mediating Wnt Signaling. Molecular Cancer, 19, Article No. 3. https://doi.org/10.1186/s12943-019-1128-6

  34. 34. Bhan, A., Soleimani, M. and Mandal, S.S. (2017) Long Noncoding Rna and Cancer: A New Paradigm. Cancer Research, 77, 3965-3981. https://doi.org/10.1158/0008-5472.CAN-16-2634

  35. 35. Chu, C., Zhang, Q.C., da Rocha, S.T., Flynn, R.A., Bharadwaj, M., Calabrese, J.M., et al. (2015) Systematic Discovery of Xist RNA Binding Proteins. Cell, 161, 404-416. https://doi.org/10.1016/j.cell.2015.03.025

  36. 36. Monfort, A., Minin, D.G., Postlmayr, A., Freimann, R., Arieti, F., Thore, S., et al. (2015) Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells. Cell Reports, 12, 554-561. https://doi.org/10.1016/j.celrep.2015.06.067

  37. 37. Patil, D.P., Chen, C.-K., Pickering, B.F., Chow, A., Jackson, C., Guttman, M., et al. (2016) m6A RNA Methylation Promotes XIST-Mediated Transcriptional Repression. Nature, 537, 369-373. https://doi.org/10.1038/nature19342

  38. 38. Nesterova, T.B., Wei, G., Coker, H., Pintacuda, G., Bowness, J.S., Zhang, T., et al. (2019) Systematic Allelic Analysis Defines the Interplay of Key Pathways in X Chromosome In-activation. Nature Communications, 10, Article No. 3129. https://doi.org/10.1038/s41467-019-11171-3

  39. 39. Liu, J., Zhang, X., Chen, K., Cheng, Y., Liu, S., Xia, M., et al. (2019) CCR7 Chemokine Receptor-Inducible lnc-Dpf3 Restrains Dendritic Cell Migration by Inhibiting HIF-1α-Mediated Glycolysis. Immunity, 50, 600-615. e15. https://doi.org/10.1016/j.immuni.2019.01.021

  40. 40. Liu, H., Xu, Y., Yao, B., Sui, T., Lai, L. and Li, Z. (2020) A Novel N6-Methyladenosine (m6A)-Dependent Fate Decision for the lncRNA THOR. Cell Death & Disease, 11, Article No. 613. https://doi.org/10.1038/s41419-020-02833-y

  41. 41. Fatica, A. and Bozzoni, I. (2014) Long Non-Coding RNAs: New Players in Cell Differentiation and Development. Nature Reviews Genetics, 15, 7-21. https://doi.org/10.1038/nrg3606

  42. 42. Cao, P.W., Liu, L., Li, Z.H., Cao, F. and Liu, F.B. (2022) Prognostic Value of Drug Targets Predicted Using Deep Bioinformatic Analysis of m6A-Associated lncRNA-Based Pancreatic Cancer Model Characteristics and Its Tumour Microenvironment. Frontiers in Genetics, 13, Article ID: 853471. https://doi.org/10.3389/fgene.2022.853471

  43. 43. Hu, X., Peng, W., Zhou, H., Jiang, J., Zhou, X., Huang, D., et al. (2020) IGF2BP2 Regulates DANCR by Serving as an N6-Methyladenosine Reader. Cell Death & Differentiation, 27, 1782-1794. https://doi.org/10.1038/s41418-019-0461-z

  44. 44. Chen, H., Zhuo, Q., Ye, Z., Xu, X. and Ji, S. (2021) Organoid Model: A New Hope for Pancreatic Cancer Treatment? Biochimica et Biophysica Acta (BBA)—Reviews on Cancer, 1875, Article ID: 188466. https://doi.org/10.1016/j.bbcan.2020.188466

  45. 45. Wang, H., Zhao, X. and Lu, Z. (2021) m6A RNA Methylation Regulators Act as Potential Prognostic Biomarkers in Lung Adenocarcinoma. Frontiers in Genetics, 12, Article 622233. https://doi.org/10.3389/fgene.2021.622233

  46. 46. Shen, J., Feng, X.P., Hu, R.B., et al. (2021) N-Methyladenosine Reader YTHDF2-Mediated Long Noncoding RNA FENDRR Degradation Promotes Cell Proliferation in Endometrioid Endometrial Carcinoma. Laboratory Investigation, 101, 775-784. https://doi.org/10.1038/s41374-021-00543-3

  47. 47. Ban, Y., Tan, P., Cai, J., et al. (2020) LNCAROD Is Stabilized by m6A Methylation and Promotes Cancer Progression via Forming a Ternary Complex with HSPA1A and YBX1 in Head and Neck Squamous Cell Carcinoma. Molecular Oncology, 14, 1282-1296. https://doi.org/10.1002/1878-0261.12676

    48. NOTES

    *通讯作者。

期刊菜单