设为首页 加入收藏 期刊导航 网站地图

Advances in Clinical Medicine
Vol. 13  No. 11 ( 2023 ), Article ID: 75733 , 7 pages
10.12677/ACM.2023.13112550

长链非编码RNA与肺癌预后关系研究进展

王星圆，祖拉丽阿依·阿米尔，戴月梅*

新疆医科大学第一附属医院呼吸与呼吸危重症中心，新疆 乌鲁木齐

收稿日期：2023年10月21日；录用日期：2023年11月15日；发布日期：2023年11月22日

摘要

肺癌是全球最常见的癌症，发病率和死亡率高，严重影响人类健康和生命威胁。虽然近年来其治疗取得了一定进展，但非小细胞肺癌的5年生存率仍处于较低水平。长链非编码RNA (lncRNA)作为一种不能编码蛋白质的非编码RNA分子，在多种恶性肿瘤中异常表达，且与肿瘤的预后密切相关。因此，研究lncRNA在肺癌中的表达情况，寻找与非小细胞肺癌病情进展程度有关的生物学分子标志物，对改善患者预后具有重要临床意义。本文就已发现相关lncRNA与肺癌预后关系的研究进展作一综述。

关键词

长链非编码RNA，肺癌，预后，生物标志物

Research Progress on the Relationship between Long Non-Coding RNA and Prognosis of Lung Cancer

Xingyuan Wang, Zulaliayi·Amier, Yuemei Dai*

Respiratory and Respiratory Critical Care Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi Xinjiang

Received: Oct. 21st, 2023; accepted: Nov. 15th, 2023; published: Nov. 22nd, 2023

ABSTRACT

Lung cancer is the most common cancer in the world, with high morbidity and mortality, seriously affecting human health and threatening life. Although its treatment has made some progress in recent years, the 5-year survival rate of non-small cell lung cancer is still low. Long non-coding RNA (lncRNA), as a non-coding RNA molecule that cannot encode protein, is abnormally expressed in a variety of malignant tumors and is closely related to tumor prognosis. Therefore, studying the expression of lncRNA in lung cancer and searching for biological molecular markers related to the progression of NSCLC have important clinical significance for improving the prognosis of patients. In this review, we reviewed the research progress on the relationship between lncRNA and lung cancer prognosis.

Keywords:Long Non-Coding RNA, Lung Cancer, Prognosis, Biological Marker

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

非小细胞肺癌(non-small cell lung cancer, NSCLC)约占有所有肺癌的85%，是最常见的肺癌类型，外科根治术、放化疗、靶向治疗是其主要治疗手段，这些治疗方式提高了患者的生存率 [1] ，但很少能达到治愈肺癌的目的，全球晚期肺癌患者的5年生存率约为6% [2] 。临床病例常并发淋巴结转移与肿瘤远处转移，预后较差 [3] 。长链非编码RNA (long non-coding RNA, lncRNA)的转录长度超过200个核苷酸，由于缺乏完整的开放阅读框而无法对蛋白质进行编码 [4] ，但可直接以RNA的形式对基因的表达水平进行调控，与癌症的发生发展存在着密切联系。研究发现，lncRNA的异常表达与肿瘤侵袭转移、治疗抵抗和高死亡率密切相关，因此可能成为肿瘤潜在的预后标志及治疗靶点 [5] [6] 。多种lncRNA在肺癌组织中异常表达，lncRNA表达的上调或下调与肺癌的预后密切相关 [7] 。鉴于晚期非小细胞肺癌仍然无法治愈，有效的预后因素对于获得有关疾病发展的信息、构建同质患者群体和指导临床管理至关重要 [8] 。近年来研究者发现了较多与肺癌预后密切相关的lncRNA，现就lncRNA与肺癌预后关系的研究进展予以综述。

2. lncRNA

2.1. lncRNA的结构和功能

lncRNA是一类长度超过200个核苷酸的非编码RNA [9] ，其不具有编码蛋白质的作用，可参与各种疾病的基因表达，并影响生物过程和体内平衡。lncRNA在生物体内广泛存在，原因是其主要结构与mRNA相似，两者都包含外显子和内含子，并且与3’-多聚A尾巴、5’-帽结构具有相同的结构。此外，lncRNA的长度有助于形成相对稳定的高级结构，使它们有能力参与细胞的组织和调节 [10] 。其功能主要为：① 与某些转录因子结合成复合体，影响mRNA转录；② 介导染色体重构或组蛋白修饰、影响下游基因的表达；②通过与RNA形成互补双链，干扰mRNA的剪切；③ 作为竞争性内源RNA，竞争结合miRNA的目标mRNA；④ 与特定蛋白质结合，调节相应蛋白的活性或改变蛋白在细胞中的定位；⑤ 作为结构组分与蛋白质形成核酸蛋白质复合体；⑥ 作为小分子RNA的前体分子。

2.2. lncRNA在肿瘤中的作用

lncRNA可以通过靶向多个miRNA的表达并在转录前后激活与过程相关的不同信号通路，如表观遗传学和基因调控来调节和修改各种基因表达过程 [11] 。lncRNA可以调节细胞中的信号转导，从而促进或抑制肿瘤细胞的增殖，诱导其凋亡，并最终调节肿瘤干细胞的生长和转移。lncRNA可参与多个水平调控基因的表达，影响细胞的生长和发育，并且与肿瘤的发生、发展及预后有着密切关系。lncRNA在NSCLC组织及细胞系中异常表达，其通过刺激或抑制肿瘤细胞增殖、侵袭、迁移、凋亡及细胞周期等生物学过程来调控NSCLC的发生发展，这表明lncRNA与肿瘤的关系密切。因此，研究lncRNA与肿瘤预后的关系对肿瘤的诊治具有重要意义。

3. 与肺癌预后相关的lncRNA

3.1. 肺腺癌转移相关转录本1 (MALAT1)

MALAT1是一种基因间转录物，位于人类11q13.1染色体上，长约8.7 kb，是正常组织中最丰富的lncRNA之一，是NSCLC预后的重要指标 [12] 。MALAT1通过调节NSCLC细胞中由miR-185-5p介导的MDM4表达，促进了增殖、迁移、入侵和阻碍了凋亡 [13] 。MALAT1还抑制耐多西紫杉醇肺腺癌细胞中的miR-200b功能，通过海绵miR-200b来上调E2F转录因子3和ZEB1来调节肺腺癌细胞化学耐药性 [14] 。研究表明，MALAT1在NSCLC体内或血清中被过度诱导表达，其诱导水平与肿瘤大小、分期、转移范围和NSCLC的远距离浸润水平显著相关 [15] 。在NSCLC组织中，MALAT1的表达高于邻近组织，其表达与年龄、肿瘤大小、TNM分期有关。MALAT1表达较高的NSCLC患者的OS率较低 [16] 。因此，MALAT1可以作为NSCLC患者早期诊断、严重性评估或预后评估的生物标志物。

3.2. 浆细胞瘤转化迁移基因1 (PVT1)

PVT1定位于人类8q24染色体上，长度大于300个核苷酸，是一种新发现的lncRNA，在多种癌症中高表达，可作为癌症新型标志分子 [17] 。PVT1在NSCLC的癌组织和细胞系中表达水平显著升高，通过与miR-128内源性竞争调节血管内皮生长因子C来促进细胞增殖和转移，与肺癌的不利预后显著相关。当PVT1被放大时，肺癌患者的生存预后很差 [18] 。Xiao等发现，上调的PVT1可作为癌症患者总生存期的独立预测因子 [19] 。有研究表明，PVT1在NSCLC组织中高表达，与吸烟史、铂类耐药、TNM分期、淋巴结转移及5年生存率有关，是影响NSCLC患者不良预后的危险因素。Kaplan-Meier生存分析结果显示，PVT1高表达组患者5年总生存率显著低于低表达组，多因素Cox回归分析发现，PVT1高表达是影响NSCLC患者不良预后的独立危险因素 [20] 。

3.3. 结肠癌相关转录物2 (CCAT2)

CCAT2位于人类8q 24.21染色体上，长度约为0.34 kb，是在结肠癌中被发现的一类lncRNA，与肿瘤的形成相关 [21] 。8q24有高度保守性的区域，并具有单核苷酸多态性位点rs6983276，增加了肺癌的风险 [22] 。研究表明，肺癌细胞株及癌组织中CCAT2的表达显著较高(P < 0.05)，敲低CCAT2能够抑制H1975肺癌细胞的增殖、迁移及浸润 [23] 。CCAT2通过调控SIRT1蛋白表达激活Wnt/β-catenin信号通路进而促进肺癌细胞增殖、迁移及浸润，有望成为新的肿瘤标志物 [24] 。CCAT2高表达的小细胞肺癌患者OS明显低于CCAT2低表达组(P < 0.001)，多因素分析显示，CCAT2过表达是NSCLC患者生存不良的独立预后因素(P = 0.007) [25] 。因此，CCAT2可以作为NSCLC患者潜在的预后生物标志物。

3.4. lncRNA H19

H19是一种基因间和母体表达的lncRNA，定位于11p15.5号染色体上，长约2.3 kb，包含五个外显子和四个内含子，是哺乳动物中识别和进化保守的第一个印记基因。H19在NSCLC中上调，通过海绵miR-140-5p调节FGF9的表达，进而促进NSCLC病情进展 [26] 。H19在NSCLC的癌组织和细胞系中表达升高，与肿瘤大小和分期呈正相关，其过度表达促进了肺癌细胞的生长、迁移、入侵和上皮间充质过渡(EMT)，H19高表达的患者预后较差 [27] 。Zhou等人发现H19高表达是影响肺癌患者预后总生存期的独立危险因素[HR = 8.674, 95% CI (5.030~19.668), P < 0.001]，与NSCLC患者的临床特征密切相关，包括肿瘤大小、肿瘤分化程度、TNM分期以及淋巴结转移，其高表达伴随患者免疫功能的下降和炎症反应因子的增加，提示患者的不良预后，上调的H19患者总生存期更短 [28] 。因此，上调的H19是NSCLC潜在的预后生物标志物。

3.5. 生长停止特殊转录5 (GAS5)

GAS5位于人类1q25.1号染色体上，长约63 kb，一个与淋巴瘤相关的染色体位点，被认为是许多癌症的肿瘤抑制基因 [29] 。GAS5在NSCLC癌组织和血浆中表达水平均会下调，与临床病理分期有关，有可能作为NSCLC的诊断标志物。在功能上，GAS5参与阻止细胞生长和诱导凋亡。GAS5表达在NSCLC组织和血浆中向下调节，与NSCLC患者的预后不良有关 [30] 。GAS5通过抑制miR-221-3p提高IRF2表达水平，抑制NSCLC细胞的增殖、迁移和入侵，部分阻止了NSCLC的进展 [31] 。GAS5的过度表达通过增加E钙粘蛋白和减少N钙粘蛋白抑制肺癌细胞的增殖，通过影响EMT途径被视为抗肺癌药物 [32] 。另有研究通过检测GAS5在NSCLC癌组织中的表达量，发现GAS5在NSCLC中表达显著下降，其相对表达与肿瘤分化、TNM分期和淋巴结转移的程度相关 [33] [34] ，且GAS5高表达患者的生存率明显优于GAS5低表达的患者 [34] 。

3.6. 神经母细胞瘤相关转录物1 (NBAT1)

NBAT1也称为CASC14，位于人类6p22.3染色体上，首次在神经母细胞瘤中发现 [35] ，后发现在膀胱癌、胶质母细胞瘤、骨肉瘤等多种癌症中起肿瘤抑制作用，其低表达与肿瘤分期和淋巴结转移及预后不良有关，过表达NBAT1抑制肿瘤的增殖、迁移和侵袭 [36] 。Zheng [37] 等人首次报告说，NBAT1的表达在NSCLC细胞系中受到下调，通过调节ATG7抑制自噬表现出肿瘤抑制作用。NBAT1在NSCLC中下调，通过与miR-21-5p连接来负调节目标基因，促进癌细胞的增殖和迁移 [38] 。Wang [39] 等人发现，NBAT1表达是NSCLC患者的独立预后因素(HR =2.947, 95% CI: 1.184~4.369, P = 0.014)，单因素分析显示，淋巴结转移、TMN分期、NBAT1表达是影响NSCLC患者总生存的危险因素(P < 0.05)。生存曲线分析显示，NSCLC中NBAT1表达低的患者总体生存期明显更短(P = 0.008)。

3.7. lncRNA ZEB1反义RNA1 (ZEB1-AS1)

ZEB1-AS1具有促进肿瘤恶性生长的作用，其长度为2232 bp，首次发现于肝癌中，后续在结直肠癌、肺癌等肿瘤中也发现ZEB1-AS1表达上调，与肿瘤的预后密切相关 [40] [41] [42] 。ZEB1-AS1通过抑制NSCLC中的ID1作为癌基因影响细胞迁移和凋亡，与NSCLC的预后不良有关 [43] 。多研究表明，ZEB1-AS1在NSCLC组织中上调，沉默ZEB1-AS1抑制NSCLC细胞增殖和迁移，并促进了细胞凋亡，上调的ZEB1-AS1与肿瘤大小、淋巴结转移和TNM阶段、总体生存率较差显著相关(P < 0.05) [43] [44] 。此外，ZEB1-AS1高表达的患者OS不佳(HR = 3.202, 95% CI (2.018~5.078), P < 0.001)，多变量Cox分析表明，ZEB1-AS1高表达是NSCLC患者的独立不良预后因素 [44] 。因此，ZEB1-AS1有望成为NSCLC干预的预后生物标志物和潜在治疗目标。

3.8. HOX转录反义RNA (HOTAIR)

HOTAIR位于人类12q13.13染色体上，长约2.2 kb，包含6个外显子 [45] ，是第一个被认为具有转录调节并与恶性肿瘤相关的lncRNA。HOTAIR主要与Polycomb抑制复合物2相互作用，以调节染色体重排并促进肿瘤发生 [46] 。Zhang等人在肺癌中发现了外体HOTAIR通过海绵miR-203促进的增殖、迁移和入侵 [47] 。HOTAIR在NSCLC患者肿瘤组织和血清外切体中高度表达，其表达水平可以促进NSCLC的入侵和迁移，与淋巴结转移、肿瘤大小和TNM分期有显著相关性，外切体可通过HOTAIR运输促进NSCLC的增殖和迁移 [48] 。因此，外切体衍生的HOTAIR还有可能成为NSCLC不良预后的新分子标志物，HOTAIR的外切体传播可能为NSCLC诊断提供一种新方法。

4. 总结与展望

综上所述，多种lncRNA在肺癌组织中异常表达，与肺癌的预后密切相关。lncRNA作为肺癌发展的关键调节因素，起到癌基因(MALAT1, HOTAIR, CCAT2)或肿瘤抑制剂(GAS5, NBAT1)的作用，这些上调或下调的lncRNA与肿瘤分化、淋巴结转移、TNM分期和患者生存率显著相关。因此，lncRNA作为肺癌的生物分子标志物和靶点具有巨大潜力。虽然目前关于lncRNA与肺癌预后关系的研究较多，但有关lncRNA影响肺癌预后具体机制的研究依然很少。相信通过不断的深入研究，会发现更多与肺癌有密切关系的lncRNA，以及更多的研究成果运用于临床，肺癌患者的生存率将会提高。

文章引用

王星圆,祖拉丽阿依·阿米尔,戴月梅. 长链非编码RNA与肺癌预后关系研究进展
Research Progress on the Relationship between Long Non-Coding RNA and Prognosis of Lung Cancer[J]. 临床医学进展, 2023, 13(11): 18175-18181. https://doi.org/10.12677/ACM.2023.13112550

参考文献

  1. 1. Pawlak, K., Gabryel, P., Kujawska, A., Kasprzyk, M., Piwkowski, C., Kuffel, B. and Dyszkiewicz, W. (2018) Long-Term Results of Surgical Treatment of Non-Small Cell Lung Cancer in Patients over 75 Years of Age. Kardi-ochirugia i Torakochirurgia Polska, 15, 65-71. https://doi.org/10.5114/kitp.2018.76470

  2. 2. Siegel, R.L., Miller, K.D. and Jemal, A. (2020) Cancer Statistics, 2020. CA: A Cancer Journal for Clinicians, 70, 7-30. https://doi.org/10.3322/caac.21590

  3. 3. Liu, X., Huang, G., Zhang, J., Zhang, L. and Liang, Z. (2020) Prognostic and Clinicopathological Significance of Long Noncoding RNA MALAT-1 Expression in Patients with Non-Small Cell Lung Cancer: A Meta-Analysis. PLOS ONE, 15, e0240321. https://doi.org/10.1371/journal.pone.0240321

  4. 4. Yu, H., Shen, Z.A., Zhou, Y.K. and Du, P.F. (2022) Recent Advances in Predicting Protein-lncRNA Interactions Using Machine Learning Methods. Current Gene Therapy, 22, 228-244. https://doi.org/10.2174/1566523221666210712190718

  5. 5. Li, X., Sun, D., Zhao, T. and Zhang, Z. (2020) Long Non-Coding RNA ROR Confers Arsenic Trioxide Resistance to HepG2 Cells by Inhibiting p53 Expression. European Journal of Pharmacology, 872, Article ID: 172982. https://doi.org/10.1016/j.ejphar.2020.172982

  6. 6. Wang, X., Lai, Q., He, J., Li, Q., Ding, J., Lan, Z., Gu, C., Yan, Q., Fang, Y., Zhao, X. and Liu, S. (2019) LncRNA SNHG6 Promotes Proliferation, Invasion and Migration in Colorec-tal Cancer Cells by Activating TGF-β/Smad Signaling Pathway via Targeting UPF1 and Inducing EMT via Regulation of ZEB1. International Journal of Medical Sciences, 16, 51-59. https://doi.org/10.7150/ijms.27359

  7. 7. Sun, Z., Shao, B., Liu, Z., Dang, Q., Guo, Y., Chen, C., Guo, Y., Chen, Z., Liu, J., Hu, S., Yuan, W. and Zhou, Q. (2021) LINC01296/miR-141-3p/ZEB1-ZEB2 Axis Promotes Tumor Metastasis via Enhancing Epithelial-Mesenchymal Transi-tion Process. Journal of Cancer, 12, 2723-2734. https://doi.org/10.7150/jca.55626

  8. 8. Chen, R., Manochakian, R., James, L., Azzouqa, A.G., Shi, H., Zhang, Y., Zhao, Y., Zhou, K. and Lou, Y. (2020) Emerging Therapeutic Agents for Advanced Non-Small Cell Lung Cancer. Journal of Hematology & Oncology, 13, Article No. 58. https://doi.org/10.1186/s13045-020-00881-7

  9. 9. Li, Y., Zhang, H., Guo, J., Li, W., Wang, X., Zhang, C., Sun, Q. and Ma, Z. (2021) Downregulation of LINC01296 Suppresses Non-Small-Cell Lung Cancer via Targeting miR-143-3p/ATG2B. Acta Biochimica et Biophysica Sinica, 53, 1681-1690. https://doi.org/10.1093/abbs/gmab149

  10. 10. Wang, C., Wang, L., Ding, Y., Lu, X., Zhang, G., Yang, J., Zheng, H., Wang, H., Jiang, Y. and Xu, L. (2017) LncRNA Structural Characteristics in Epigenetic Regulation. International Jour-nal of Molecular Sciences, 18, Article 2659. https://doi.org/10.3390/ijms18122659

  11. 11. Hao, L., Wu, W., Xu, Y., Chen, Y., Meng, C., Yun, J. and Wang, X. (2023) LncRNA-MALAT1: A Key Participant in the Occurrence and Development of Cancer. Molecules, 28, Article 2126. https://doi.org/10.3390/molecules28052126

  12. 12. Sun, Y. and Ma, L. (2019) New Insights into Long Non-Coding RNA MALAT1 in Cancer and Metastasis. Cancers, 11, Article 216. https://doi.org/10.3390/cancers11020216

  13. 13. Wang, D., Zhang, S., Zhao, M. and Chen, F. (2020) LncRNA MALAT1 Accelerates Non-Small Cell Lung Cancer Progression via Regulating miR-185-5p/MDM4 Axis. Cancer Medicine, 9, 9138-9149. https://doi.org/10.1002/cam4.3570

  14. 14. Chen, J., Liu, X., Xu, Y., Zhang, K., Huang, J., Pan, B., Chen, D., Cui, S., Song, H., Wang, R., Chu, X., Zhu, X. and Chen, L. (2019) TFAP2C-Activated MALAT1 Modulates the Chemo-resistance of Docetaxel-Resistant Lung Adenocarcinoma Cells. Molecular Therapy Nucleic Acids, 14, 567-582. https://doi.org/10.1016/j.omtn.2019.01.005

  15. 15. Zhou, Q., Liu, L., Zhou, J., Chen, Y., Xie, D., Yao, Y. and Cui, D. (2021) Novel Insights into MALAT1 Function as a MicroRNA Sponge in NSCLC. Frontiers in Oncology, 11, Article 758653. https://doi.org/10.3389/fonc.2021.758653

  16. 16. Chen, W., Zhao, W., Chen, S., Zhang, L., Guo, Z., Wang, L., Wang, J., Wan, Z., Hong, Y. and Yu, L. (2018) Expression and Correlation of MALAT1 and SOX9 in Non-Small Cell Lung Cancer. The Clinical Respiratory Journal, 12, 2284-2291. https://doi.org/10.1111/crj.12906

  17. 17. Esfandi, F., Taheri, M., Omrani, M.D., Shadmehr, M.B., Arsang-Jang, S., Shams, R. and Ghafouri-Fard, S. (2019) Expression of Long Non-Coding RNAs (lncRNAs) Has Been Dysregulated in Non-Small Cell Lung Cancer Tissues. BMC Cancer, 19, Article No. 222. https://doi.org/10.1186/s12885-019-5435-5

  18. 18. Pan, Y., Liu, L., Cheng, Y., Yu, J. and Feng, Y. (2020) Amplified LncRNA PVT1 Promotes Lung Cancer Proliferation and Metastasis by Facilitating VEGFC Expression. Biochemistry and Cell Biology, 98, 676-682. https://doi.org/10.1139/bcb-2019-0435

  19. 19. Xiao, M., Feng, Y., Liu, C. and Zhang, Z. (2018) Prognostic Values of Long Noncoding RNA PVT1 in Various Carcinomas: An Updated Systematic Review and Meta-Analysis. Cell Prolifer-ation, 51, e12519. https://doi.org/10.1111/cpr.12519

  20. 20. 李靖凯, 王伟, 周冬冬. LncRNA PVT1在非小细胞肺癌中的表达及与铂类化疗敏感性的关系[J]. 热带医学杂志, 2021, 21(4): 472-476.

  21. 21. Xin, Y., Li, Z., Zheng, H., Chan, M.T.V., Ka Kei Wu, W. (2017) CCAT2: A Novel Oncogenic Long Non-Coding RNA in Human Cancers. Cell Proliferation, 50, e12342. https://doi.org/10.1111/cpr.12342

  22. 22. Yu, W.L., Yao, J.J., Xie, Z.Z., Huang, Y.J. and Xiao, S. (2021) LncRNA PRNCR1 rs1456315 and CCAT2 rs6983267 Polymorphisms on 8q24 Associated with Lung Cancer. Interna-tional Journal of General Medicine, 14, 255-266. https://doi.org/10.2147/IJGM.S290997

  23. 23. He, L., Du, Z.D., Wang, Y., Meng, R.Q. and Zhao, W.W. (2020) Ef-fects of shRNA on Cisplatin-Resistant Non-Small Cell Lung Cancer Cell A549 via Silencing CCAT2. Journal of Si-chuan University Medical Science Edition, 51, 312-319.

  24. 24. 芮文秀, 王亮歌. lncRNA CCAT2调控SIRT1蛋白表达激活Wnt/β-catenin通路影响非小细胞肺癌细胞增殖和转[J]. 中国细胞生物学学报, 2021, 43(5): 971-978.

  25. 25. Chen, S., Wu, H., Lv, N., Wang, H., Wang, Y., Tang, Q., Shao, H. and Sun, C. (2016) LncRNA CCAT2 Predicts Poor Prognosis and Regulates Growth and Metastasis in Small Cell Lung Cancer. Biomedicine & Pharma-cotherapy, 82, 583-588. https://doi.org/10.1016/j.biopha.2016.05.017

  26. 26. Li, X., Lv, F., Li, F., Du, M., Liang, Y., Ju, S., Liu, Z., Wang, B. and Gao, Y. (2020) Long Non Coding RNA H19 Facilitates Small Cell Lung Cancer Tumor-igenesis through miR-140-5p/FGF9 Axis. OncoTargets and Therapy, 13, 3525-3534. https://doi.org/10.2147/OTT.S245710

  27. 27. Zhou, Y. and Xia, Q. (2022) LncRNA H19 Promotes Lung Adenocar-cinoma Progression via Binding to Mutant p53 R175H. Cancers, 14, Article 4486. https://doi.org/10.3390/cancers14184486

  28. 28. 周建英, 刘震天, 胡珍珍, 等. 肺癌组织中长链非编码RNA-H9的表达与患者免疫功能、炎症反应因子及预后的关系[J]. 中国免疫学杂志, 2021, 37(16): 2012-2016.

  29. 29. Ni, W., Yao, S., Zhou, Y., Liu, Y., Huang, P., Zhou, A., Liu, J., Che, L. and Li, J. (2019) Long Noncoding RNA GAS5 Inhibits Progression of Colorectal Cancer by Interacting with and Triggering YAP Phosphorylation and Degradation and Is Neg-atively Regulated by the m6A Reader YTHDF3. Molecular Cancer, 18, Article No. 143. https://doi.org/10.1186/s12943-019-1079-y

  30. 30. Al Mourgi, M., El Askary, A., Gharib, A.F., Alzahrani, R., Ban-jer, H.J., Elsawy, W.H., Al, A.E. and Raafat, N. (2021) Circulating Long Non-Coding RNA GAS5: A Non-Invasive Molecular Marker for Prognosis, Response to Treatment and Survival in Non-Small Cell Lung Cancer. Cancer Investi-gation, 39, 505-513. https://doi.org/10.1080/07357907.2021.1928167

  31. 31. Ma, J., Miao, H., Zhang, H., Ren, J., Qu, S., Da, J., Xu, F. and Zhao, H. (2021) LncRNA GAS5 Modulates the Progression of Non-Small Cell Lung Cancer through Repressing miR-221-3p and Up-Regulating IRF2. Diagnostic Pathology, 16, Article No. 46. https://doi.org/10.1186/s13000-021-01108-0

  32. 32. Zhu, L., Zhou, D., Guo, T., Chen, W., Ding, Y., Li, W., Huang, Y., Huang, J. and Pan, X. (2021) LncRNA GAS5 Inhibits Invasion and Migration of Lung Cancer through Influencing EMT Process. Journal of Cancer, 12, 3291-3298. https://doi.org/10.7150/jca.56218

  33. 33. Yang, X., Meng, L., Zhong, Y., Hu, F., Wang, L. and Wang, M. (2021) The Long Intergenic Noncoding RNA GAS5 Reduces Cisplatin-Resistance in Non-Small Cell Lung Cancer through the miR-217/LHPP Axis. Aging, 13, 2864-2884. https://doi.org/10.18632/aging.202352

  34. 34. Fu, Y., Liu, L., Zhan, J., Zhan, H. and Qiu, C. (2021) LncRNA GAS5 Expression in Non-Small Cell Lung Cancer Tissues and Its Correlation with Ki67 and EGFR. American Journal of Translational Research, 13, 4900-4907.

  35. 35. Wei, L., Ling, M., Yang, S., Xie, Y., Liu, C. and Yi, W. (2021) Long Noncoding RNA NBAT1 Suppresses Hepatocellular Carcinoma Progression via Competitively Associating with IGF2BP1 and Decreasing c-Myc Expression. Human Cell, 34, 539-549. https://doi.org/10.1007/s13577-020-00464-1

  36. 36. Yan, J., Huang, W., Huang, X., Xiang, W., Ye, C. and Liu, J. (2018) A Negative Feedback Loop between Long Noncoding RNA NBAT1 and Sox9 Inhibits the Malignant Progres-sion of Gastric Cancer Cells. Bioscience Reports, 38, BSR20180882. https://doi.org/10.1042/BSR20180882

  37. 37. Zheng, T., Li, D., He, Z., Feng, S. and Zhao, S. (2018) Long Noncod-ing RNA NBAT1 Inhibits Autophagy via Suppression of ATG7 in Non-Small Cell Lung Cancer. American Journal of Cancer Research, 8, 1801-1811.

  38. 38. Lv, D., Bi, Q., Li, Y., Deng, J., Wu, N., Hao, S. and Zhao, M. (2021) Long Non-Coding RNA MEG3 Inhibits Cell Migration and Invasion of Non-Small Cell Lung Cancer Cells by Regulating the miR-21-5p/PTEN Axis. Molecular Medicine Reports, 23, Article No. 191. https://doi.org/10.3892/mmr.2021.11830

  39. 39. Wang, D.L., Yuan, P. and Tian, J.Y. (2020) Expression of Long Noncoding RNA NBAT1 Is Associated with the Outcome of Patients with Non-Small Cell Lung Cancer. Revista da As-sociação Médica Brasileira, 66, 898-903. https://doi.org/10.1590/1806-9282.66.7.898

  40. 40. Xue, S., Lu, F., Sun, C., Zhao, J., Zhen, H. and Li, X. (2021) LncRNA ZEB1-AS1 Regulates Hepatocellular Carcinoma Progression by Targeting miR-23c. World Journal of Surgical Oncology, 19, Article No. 121. https://doi.org/10.1186/s12957-021-02176-8

  41. 41. Ruan, L., Chen, W., Zhao, X., Fang, N. and Li, T. (2022) Pre-dictive Potentials of ZEB1-AS1 in Colorectal Cancer Prognosis and Their Correlation with Immunotherapy. Journal of Oncology, 2022, Article ID: 1084555. https://doi.org/10.1155/2022/1084555

  42. 42. Wang, J., Han, X., Yuan, Y., Gu, H., Liao, X. and Jiang, M. (2022) The Value of Dysregulated LncRNAs on Clinicopathology and Survival in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Frontiers in Genetics, 13, Article 821675. https://doi.org/10.3389/fgene.2022.821675

  43. 43. Jin, J., Wang, H., Si, J., Ni, R., Liu, Y. and Wang, J. (2019) ZEB1-AS1 Is Associated with Poor Prognosis in Non-Small-Cell Lung Cancer and Influences Cell Migration and Apoptosis by Repressing ID1. Clinical Science, 133, 381-392. https://doi.org/10.1042/CS20180983

  44. 44. Xie, J., Wu, Y., Bian, X., Chen, D., Gui, Q. and Huang, J. (2018) In-creased Expression of lncRNA ZEB1-AS1 in Non-Small Cell Lung Cancer Is Associated with Poor Prognosis. Interna-tional Journal of Clinical and Experimental Pathology, 11, 3703-3707.

  45. 45. Xin, X., Li, Q., Fang, J. and Zhao, T. (2021) LncRNA HOTAIR: A Potential Prognostic Factor and Therapeutic Target in Human Cancers. Frontiers in On-cology, 11, Article 679244. https://doi.org/10.3389/fonc.2021.679244

  46. 46. Li, S., Xiong, Q., Chen, M., Wang, B., Yang, X., Yang, M., Wang, Q., Cui, Z. and Ge, F. (2021) Long Noncoding RNA HOTAIR Interacts with Y-Box Pro-tein-1 (YBX1) to Regulate Cell Proliferation. Life Science Alliance, 4, e202101139. https://doi.org/10.26508/lsa.202101139

  47. 47. Zhang, C., Xu, L., Deng, G., Ding, Y., Bi, K., Jin, H., Shu, J., Yang, J., Deng, H., Wang, Z. and Wang, Y. (2020) Exosomal HOTAIR Promotes Proliferation, Migration and Invasion of Lung Cancer by Sponging miR-203. Science China Life Sciences, 63, 1265-1268. https://doi.org/10.1007/s11427-019-1579-x

  48. 48. Chen, L., Huang, S., Huang, J., Chen, Q. and Zhuang, Q. (2021) Role and Mechanism of Exosome-Derived Long Noncoding RNA HOTAIR in Lung Cancer. ACS Omega, 6, 17217-17227. https://doi.org/10.1021/acsomega.1c00905

    49. NOTES

    *通讯作者。

期刊菜单