国际医药卫生导报 ›› 2025, Vol. 31 ›› Issue (20): 3389-3395.DOI: 10.3760/cma.j.cn441417-20250410-20010
lncRNA在食管癌中的作用机制研究进展
林宇宁 谢鸿燕 赵文镇 张忠英 金宏伟
厦门弘爱医院医学检验中心,厦门 361000
收稿日期:2025-04-10
出版日期:2025-10-15
发布日期:2025-10-27
通讯作者:
张忠英,Email:zhangzy1121@xmu.edu.cn;金宏伟,Email:jinhw@haxm.com
基金资助:厦门市自然科学基金(3502Z20227389)
Research progress on mechanism of roles of lncRNA in esophageal cancer
Lin Yuning, Xie Hongyan, Zhao Wenzhen, Zhang Zhongying, Jin Hongwei
Medical Laboratory, Xiamen Humanity Hospital, Xiamen 361000, China
Received:2025-04-10
Online:2025-10-15
Published:2025-10-27
Contact:
Zhang Zhongying, Email: zhangzy1121@xmu.edu.cn; Jin Hongwei, Email: jinhw@haxm.com
Supported by:Xiamen Natural Science Foundation (3502Z20227389)
摘要:
食管癌是消化系统里高发且危险的恶性肿瘤之一,在亚洲地区更为常见。它的发病是受多种因素影响、历经多个阶段、涉及多个基因参与的复杂病理过程,环境因素、生活习惯、慢性炎症、遗传易感性以及分子机制等共同参与其中。近年,长链非编码RNA(long non-coding RNA,lncRNA)作为关键调控因子在食管癌中发挥的作用备受瞩目。lncRNA是一类长度超过200个核苷酸的非编码RNA,其调控基因表达的方式多样,涵盖表观遗传修饰、竞争性内源RNA网络、RNA-蛋白相互作用等机制。研究发现,在食管癌中,lncRNA参与调控肿瘤细胞诸多关键生物学过程,如增殖、侵袭、转移、凋亡、耐药性、放射抗性、干细胞特性以及上皮-间质转化(epithelial-mesenchymal transition,EMT)等。本综述全面梳理了lncRNA在食管癌病理生理学中的广泛调控作用及潜在的临床价值,着重阐述了其参与的调控轴在食管癌中的具体作用,为未来深入探究lncRNA的分子机制和临床转化应用提供方向,也为改善食管癌患者预后、探寻治疗靶点提供新的思路。
林宇宁 谢鸿燕 赵文镇 张忠英 金宏伟.
lncRNA在食管癌中的作用机制研究进展 [J]. 国际医药卫生导报, 2025, 31(20): 3389-3395.
Lin Yuning, Xie Hongyan, Zhao Wenzhen, Zhang Zhongying, Jin Hongwei.
Research progress on mechanism of roles of lncRNA in esophageal cancer [J]. International Medicine and Health Guidance News, 2025, 31(20): 3389-3395.
| [1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3):229-263. DOI: 10.3322/caac.21834. [2] Teng Y, Xia C, Cao M, et al. Esophageal cancer global burden profiles, trends, and contributors[J]. Cancer Biol Med, 2024, 21(8):656–666. DOI: 10.20892/j.issn.2095-3941.2024.0145. [3] Yokoyama A, Kakiuchi N, Yoshizato T, et al. Age-related remodelling of oesophageal epithelia by mutated cancer drivers[J]. Nature, 2019, 565(7739):312-317. DOI: 10.1038/s41586-018-0811-x. [4] Zhuang P, Wu F, Liu X, et al. Preserved vegetable consumption and its association with mortality among 440,415 people in the China Kadoorie Biobank[J]. BMC Med, 2023, 21(1):135. DOI: 10.1186/s12916-023-02829-3. [5] 张嫣然,宇传华,胡迪,等. 1990-2019年中国归因于水果摄入不足的食管癌死亡趋势[J]. 中华疾病控制杂志,2023,27(1):4-10. DOI:10.16462/j.cnki.zhjbkz.2023.01.002. [6] Wong MCS, Deng Y, Huang J, et al. Performance of screening tests for esophageal squamous cell carcinoma: a systematic review and meta-analysis[J]. Gastrointest Endosc, 2022, 96(2):197-207.e34. DOI: 10.1016/j.gie.2022.04.005. [7] Min Q, Zhang M, Lin D, et al. Genomic characterization and risk stratification of esophageal squamous dysplasia [J]. Med Rev (2021), 2024, 4(3): 244-256. DOI: 10.1515/mr-2024-0008. [8] Vassilenko V, Moura PC, Raposo M. Diagnosis of carcinogenic pathologies through breath biomarkers: present and future trends[J]. Biomedicines, 2023, 11(11): 3029. DOI: 10.3390/biomedicines11113029. [9] 冯绪梅,宋相庆,季冠虹,等. 血浆外泌体miR-548k在食管鳞癌中的表达及诊断价值[J]. 山东大学学报(医学版),2024,62(5):79-88. DOI: 10.6040/j.issn.1671-7554.0.2024.0134. [10] Wang X, Yu N, Cheng G, et al. Prognostic value of circulating tumour DNA during post-radiotherapy surveillance in locally advanced esophageal squamous cell carcinoma[J]. Clin Transl Med, 2022,12(11): e1116. DOI: 10.1002/ctm2.1116. [11] 赵文镇,林宇宁. LINC01836是一种新的结直肠癌诊断和预后的生物标志物[J]. 国际医药卫生导报,2022,28(3):363-367. DOI: 10.3760/cma.j.issn.1007-1245.2022.03.017. [12] 蔡灿锋,李锦宏,辛海洋,等. 直肠癌新辅助放化疗疗效lncRNA分子预测模型构建[J]. 国际医药卫生导报,2024,30(19):3170-3175. DOI:10.3760/cma.j.issn.1007-1245.2024.19.001. [13] Bridges MC, Daulagala AC, Kourtidis A. LNCcation: lncRNA localization and function[J]. J Cell Biol, 2021, 220(2):e202009045. DOI: 10.1083/jcb.202009045. [14] Fu H, Wang T, Kong X, et al. A nodal enhanced micropeptide NEMEP regulates glucose uptake during mesendoderm differentiation of embryonic stem cells[J]. Nat Commun, 2022,13(1):3984. DOI: 10.1038/s41467-022-31762-x. [15] Jia J, Li H, Chu J, et al. LncRNA FAM83A-AS1 promotes ESCC progression by regulating miR-214/CDC25B axis[J]. J Cancer, 2021, 12(4):1200-1211. DOI: 10.7150/jca.54007. [16] Han B, Ma Y, Yang P, et al. Novel histone acetylation-related lncRNA signature for predicting prognosis and tumor microenvironment in esophageal carcinoma[J]. Aging (Albany NY), 2024, 16(6):5163-5183. DOI: 10.18632/aging.205636. [17] Chen MJ, Deng J, Chen C, et al. LncRNA H19 promotes epithelial mesenchymal transition and metastasis of esophageal cancer via STAT3/EZH2 axis[J]. Int J Biochem Cell Biol, 2019, 113:27-36. DOI: 10.1016/j.biocel.2019.05.011. [18] 秦玉萍,曹通,许颖,等.敲低lncRNA CACNA1C-AS2促进上皮间质转化增强人食管癌细胞的增殖、侵袭和迁移[J].细胞与分子免疫学杂志,2023,39(3):249-257. [19] Xu J, Liu X, Liu X, et al. noncoding RNA KCNMB2-AS1 promotes the development of esophageal cancer by modulating the miR-3194-3p/PYGL axis[J]. Bioengineered, 2021, 12(1):6687-6702. DOI: 10.1080/21655979.2021.1973775. [20] Wang J, Zhang Z, Song L, et al. Inhibition of esophageal squamous cell carcinoma progression by MIR210HG and activation of the P53 signaling pathway to promote apoptosis and autophagy[J]. Eur J Med Res, 2025, 30(1):269. DOI: 10.1186/s40001-025-02512-8. [21] Tuersong T, Shataer M, Chen Y, et al. Extracellular vesicle-lncRNA HOTAIR modulates esophageal cancer chemoresistance and immune microenvironment via miR-375/CDH2 pathway[J]. J Cell Commun Signal, 2025, 19(2): e70014. DOI: 10.1002/ccs3.70014. [22] Plath K, Fang J, Mlynarczyk-Evans SK, et al. Role of histone H3 lysine 27 methylation in X inactivation[J]. Science, 2003, 300(5616):131-135. DOI: 10.1126/science.1084274. [23] Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals[J]. Nature, 2009,458(7235):223-227. DOI: 10.1038/nature07672. [24] Rinn JL, Kertesz M, Wang JK, et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs[J]. Cell, 2007, 129(7):1311-1323. DOI: 10.1016/j.cell.2007.05.022. [25] Rinn JL, Chang HY. Genome regulation by long noncoding RNAs[J]. Annu Rev Biochem, 2012,81:145-66. DOI: 10.1146/annurev-biochem-051410-092902. [26] Ao YQ, Gao J, Jiang JH, et al. Comprehensive landscape and future perspective of long noncoding RNAs in non-small cell lung cancer: it takes a village[J]. Mol Ther, 2023, 31(12):3389-3413. DOI: 10.1016/j.ymthe.2023.09.015. [27] Huarte M. The emerging role of lncRNAs in cancer[J]. Nat Med, 2015, 21(11): 1253-1261. DOI: 10.1038/nm.3981. [28] Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways [J]. Cancer Cell, 2016, 29(4): 452-463. DOI: 10.1016/j.ccell.2016.03.010. [29] Bhan A, Mandal SS. Long noncoding RNAs: emerging stars in gene regulation, epigenetics and human disease[J]. ChemMedChem, 2014, 9(9):1932-1956. DOI: 10.1002/cmdc.201300534. [30] Chen Z, Tang W, Ye W, et al. ADAMTS9-AS2 regulates PPP1R12B by adsorbing miR-196b-5p and affects cell cycle-related signaling pathways inhibiting the malignant process of esophageal cancer[J]. Cell Cycle, 2022, 21(16): 1710-1725. DOI: 10.1080/15384101.2022.2067675. [31] Wu J, Liu Y, Huang X, et al. LncRNA DGCR5 silencing enhances the radio-sensitivity of human esophageal squamous cell carcinoma via negatively regulating the warburg effect[J]. Radiat Res, 2023, 199(3): 264-272. DOI: 10.1667/RADE-22-00126.1. [32] Liu JQ, Deng M, Xue NN, et al. lncRNA KLF3-AS1 suppresses cell migration and invasion in ESCC by impairing miR-185-5p-targeted KLF3 inhibition [J]. Mol Ther Nucleic Acids, 2020, 20: 231-241. DOI: 10.1016/j.omtn.2020.01.020. [33] Chen L, Lu J, Li X, et al. LncRNA KTN1-AS1 facilitates esophageal squamous cell carcinoma progression via miR-885-5p/STRN3 axis[J]. Genes Genomics, 2024, 46(2): 241-252. DOI: 10.1007/s13258-023-01451-0. [34] Zhong YB, Shan AJ, Lv W, et al. Long non-coding RNA LINC00675 inhibits tumorigenesis and EMT via repressing Wnt/β-catenin signaling in esophageal squamous cell carcinoma[J]. Eur Rev Med Pharmacol Sci, 2018, 22(23): 8288-8297. DOI: 10.26355/eurrev_201812_16526. [35] Li P, Ding H, Han S, et al. Long noncoding RNA LINC00858 aggravates the progression of esophageal squamous cell carcinoma via regulating the miR-425-5p/ABL2 axis[J]. Heliyon, 2024,10(6): e27337. DOI: 10.1016/j.heliyon.2024.e27337. [36] Hu D, Ma A, Lu H, et al. LINC00963 promotes cisplatin resistance in esophageal squamous cell carcinoma by interacting with miR-10a to upregulate SKA1 expression[J]. Appl Biochem Biotechnol, 2024, 196(10):7219-7232. DOI: 10.1007/s12010-024-04897-4. [37] Zhao F, Tian H, Wang Y, et al. LINC01004-SPI1 axis-activated SIGLEC9 in tumor-associated macrophages induces radioresistance and the formation of immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma[J]. Cancer Immunol Immunother, 2023, 72(6):1835-1851. DOI: 10.1007/s00262-022-03364-5. [38] Liang F, Luo Q, Han H, et al. Long noncoding RNA LINC01088 inhibits esophageal squamous cell carcinoma progression by targeting the NPM1-HDM2-p53 axis[J]. Acta Biochim Biophys Sin (Shanghai), 2023, 55(3):367-381. DOI: 10.3724/abbs.2023021. [39] Zhang Y, Miao Y, Shang M, et al. LincRNA-p21 leads to G1 arrest by p53 pathway in esophageal squamous cell carcinoma[J]. Cancer Manag Res, 2019,11:6201-14. DOI: 10.2147/cmar.S197557. [40] Xiao Y, Tang J, Yang D, et al. Long noncoding RNA LIPH-4 promotes esophageal squamous cell carcinoma progression by regulating the miR-216b/IGF2BP2 axis[J]. Biomark Res, 2022, 10(1):60. DOI: 10.1186/s40364-022-00408-x. [41] Cheng W, Shi X, Lin M, et al. LncRNA MAGI2-AS3 overexpression sensitizes esophageal cancer cells to irradiation through down-regulation of HOXB7 via EZH2[J]. Front Cell Dev Biol, 2020, 8:552822. DOI: 10.3389/fcell.2020.552822. [42] Zhang S, Zhong J, Guo D, et al. MIAT shuttled by tumor-secreted exosomes promotes paclitaxel resistance in esophageal cancer cells by activating the TAF1/SREBF1 axis[J]. J Biochem Mol Toxicol, 2023, 37(8): e23380. DOI: 10.1002/jbt.23380. [43] Chu J, Li H, Xing Y, et al. LncRNA MNX1-AS1 promotes progression of esophageal squamous cell carcinoma by regulating miR-34a/SIRT1 axis[J]. Biomed Pharmacother, 2019, 116: 109029. DOI: 10.1016/j.biopha.2019.109029. [44] Wang Y, Wang Y, Zhang J, et al. LncRNA NONHSAT227443.1 confers esophageal squamous cell carcinoma chemotherapy resistance by activating PI3K/AKT signaling via targeting MRTFB[J]. Technol Cancer Res Treat, 2024, 23: 15330338241274369. DOI: 10.1177/15330338241274369. [45] Xu T, Yan Z, Lu J, et al. Long non-coding RNA NRSN2-AS1, transcribed by SOX2, promotes progression of esophageal squamous cell carcinoma by regulating the ubiquitin-degradation of PGK1[J]. Clin Exp Metastasis, 2022, 39(5): 757-769. DOI: 10.1007/s10585-022-10174-7. [46] Huang L, Wang Y, Chen J, et al. Long noncoding RNA PCAT1, a novel serum-based biomarker, enhances cell growth by sponging miR-326 in oesophageal squamous cell carcinoma [J]. Cell Death Dis, 2019, 10(7): 513. DOI: 10.1038/s41419-019-1745-4. [47] Huang T, You Q, Huang D, et al. A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma[J]. Cell Commun Signal, 2024, 22(1): 60. DOI: 10.1186/s12964-024-01475-3. [48] Yao GL, Pan CF, Xu H, et al. Long noncoding RNA RP11-766N7.4 functions as a tumor suppressor by regulating epithelial-mesenchymal transition in esophageal squamous cell carcinoma[J]. Biomed Pharmacother, 2017, 88: 778-785. DOI: 10.1016/j.biopha.2017.01.124. [49] Xu LJ, Yu XJ, Wei B, et al. LncRNA SNHG7 promotes the proliferation of esophageal cancer cells and inhibits its apoptosis [J]. Eur Rev Med Pharmacol Sci, 2018, 22(9): 2653-2661. DOI: 10.26355/eurrev_201805_14961. [50] Chang ZW, Jia YX, Zhang WJ, et al. LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1[J]. J Exp Clin Cancer Res, 2018, 37(1): 56. DOI: 10.1186/s13046-018-0724-4. [51] Guo B, He M, Ma M, et al. Long non-coding RNA X-inactive specific transcript promotes esophageal squamous cell carcinoma progression via the microRNA 34a/Zinc finger E-box-binding homeobox 1 pathway[J]. Dig Dis Sci, 2024, 69(4):1169-1181. DOI: 10.1007/s10620-024-08269-0. [52] Sahebi R, Malakootian M, Balalaee B, et al. Linc-ROR and its spliced variants 2 and 4 are significantly up-regulated in esophageal squamous cell carcinoma[J]. Iran J Basic Med Sci, 2016, 19(10): 1131-1135. [53] Wang Z, Liu XC, Gao ZG, et al. FOXD2-AS1 is modulated by METTL3 with the assistance of YTHDF1 to affect proliferation and apoptosis in esophageal cancer[J]. Acta Pharm, 2025, 75(1): 69-86. DOI: 10.2478/acph-2025-0009. [54] Wang Z, Li K, Zhang X, et al. LINC00942 accelerates esophageal cancer progression by raising PRKDC through interaction with PTBP1[J]. J Biochem Mol Toxicol, 2025, 39(3): e70220. DOI: 10.1002/jbt.70220. [55] Xue Y, Yang R, Gong P, et al. lncRNA FENDRR predicts adverse prognosis and regulates the development of esophageal squamous cell carcinoma through negatively modulating miR-495-3p[J]. Turk J Gastroenterol, 2025, 20. DOI: 10.5152/tjg.2025.24350. [56] Tang Z, Jiang Y, Zong Y, et al. LncRNA SSTR5-AS1 promotes esophageal carcinoma through regulating ITGB6/JAK1/STAT3 signaling[J]. Epigenomics, 2024,16(17):1133-1148. DOI: 10.1080/17501911.2024.2388018. [57] Shi X, Zhang X, Huang X, et al. N6-methyladenosine-mediated upregulation of LNCAROD confers radioresistance in esophageal squamous cell carcinoma through stabilizing PARP1[J]. Clin Transl Med, 2024, 14(10):e70039. DOI: 10.1002/ctm2.70039. [58] Wu K, Wang Z, Huang Y, et al. LncRNA PTPRG-AS1 facilitates glycolysis and stemness properties of esophageal squamous cell carcinoma cells through miR-599/PDK1 axis[J]. J Gastroenterol Hepatol, 2022, 37(3):507-517. DOI: 10.1111/jgh.15719. [59] 赵舒雅,李航,樊赛军. LncRNA调控肿瘤细胞辐射敏感性作用的研究进展[J]. 国际放射医学核医学杂志,2021,45(11):701-709. DOI:10.3760/cma.j.cn121381-202101027-00116. [60] Kirkeby A, Main H, Carpenter M. Pluripotent stem-cell-derived therapies in clinical trial: a 2025 update[J]. Cell Stem Cell, 2025, 32(1):10-37. DOI: 10.1016/j.stem.2024.12.005. [61] 吴漫,刘亚萍. 长链非编码RNA在调控EMT及肿瘤侵袭转移中的作用[J]. 中国细胞生物学学报,2023,45(3):405-411. DOI:10.11844/cjcb.2023.03.0007. |
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