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广西师范大学学报(自然科学版) ›› 2024, Vol. 42 ›› Issue (3): 189-197.doi: 10.16088/j.issn.1001-6600.2023013001
郑婉华1,2, 莫斯萍1, 周祖平1,2,3, 蒲仕明1,2,3*
ZHENG Wanhua1,2, MO Siping1, ZHOU Zuping1,2,3, PU Shiming1,2,3*
摘要: Nr4a3(nuclear receptor subfamily 4 group a member 3)属于核受体亚家族成员,参与细胞增殖、细胞迁移和细胞凋亡的调控。据报道,Nr4a3在多种肿瘤组织中表达下调。为探索Nr4a3在乳腺癌发生、发展中的作用,本文利用公共数据库分析NR4A3在乳腺癌组织中的表达以及与乳腺癌患者总生存率的关系。在4T1细胞系上敲除Nr4a3基因,通过流式细胞术等检测细胞凋亡、细胞周期;CCK-8与集落形成实验检测细胞活力;细胞划痕与侵袭检测细胞迁移与侵袭能力;通过q-PCR检测细胞周期和凋亡基因的表达水平。结果表明:Nr4a3在乳腺癌组织中表达水平显著下调;与乳腺癌患者的总生存率呈正相关关系;Nr4a3敲除后,细胞增殖增强,细胞凋亡减少及细胞迁移能力和侵袭能力增强。本研究揭示了Nr4a3在乳腺癌细胞增殖、凋亡、迁移和侵袭的潜在作用,可能成为乳腺癌潜在的治疗靶点。
中图分类号: R737.9
[1] MULLICAN S E, ZHANG S, KONOPLEVA M, et al. Abrogation of nuclear receptors Nr4a3 and Nr4a1 leads to development of acute myeloid leukemia[J]. Nature Medicine, 2007, 13(6): 730-735. DOI: 10.1038/nm1579. [2] BEARD J A, TENGA A, CHEN T S. The interplay of NR4A receptors and the oncogene-tumor suppressor networks in cancer[J]. Cellular Signalling, 2015, 27(2): 257-266. DOI: 10.1016/j.cellsig.2014.11.009. [3] 焦婷. 孤儿核受体NR4A1(Nur77)和NR4A3(Nor1)在急性白血病(AL)中的表达及意义[D]. 石家庄:河北医科大学, 2009. [4] DEYOUNG R A, BAKER J C, CADO D, et al. The orphan steroid receptor Nur77 family member Nor-1 is essential for early mouse embryogenesis[J]. Journal of Biological Chemistry, 2003, 278(47): 47104-47109. DOI: 10.1074/jbc.M307496200. [5] PONNIO T, BURTON Q, PEREIRA F A, et al. The nuclear receptor Nor-1 is essential for proliferation of the semicircular canals of the mouse inner ear[J]. Molecular and Cellular Biology, 2002, 22(3): 935-945. DOI: 10.1128/MCB.22.3.935-945.2002. [6] YEH C M, CHANG L Y, LIN S H, et al. Epigenetic silencing of the NR4A3 tumor suppressor, by aberrant JAK/STAT signaling, predicts prognosis in gastric cancer[J]. Scientific Reports, 2016, 6: 31690. DOI: 10.1038/srep31690. [7] KATSURA C, OGUNMWONYI I, KANKAM H K, et al. Breast cancer: presentation, investigation and management[J]. British Journal of Hospital Medicine, 2022, 83(2): 1-7. DOI: 10.12968/hmed.2021.0459. [8] TRAPANI D, GINSBURG O, FADELU T, et al. Global challenges and policy solutions in breast cancer control[J]. Cancer Treatment Reviews, 2022, 104: 102339. DOI: 10.1016/j.ctrv.2022.102339. [9] 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[J]. CA: A Cancer Journal for Clinicians, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660. [10] HUPPERT L A, MARIOTTI V, CHIEN A J, et al. Emerging immunotherapeutic strategies for the treatment of breast cancer [J]. Breast Cancer Research and Treatment, 2022, 191(2): 243-255. DOI: 10.1007/s10549-021-06406-1. [11] SINGH K, YADAV D, JAIN M, et al. Immunotherapy for breast cancer treatment: current evidence and therapeutic options[J]. Endocrine, Metabolic & Immune Disorders Drug Targets, 2022, 22(2): 212-224. DOI: 10.2174/1871530321666210426125904. [12] YOUSEFI H, FONG J, ALAHARI S K. NR4A family genes: a review of comprehensive prognostic and gene expression profile analysis in breast cancer[J]. Frontiers in Oncology, 2022, 12: 777824. DOI: 10.3389/fonc.2022.777824. [13] 郭善娴, 黄先明, 蔡勇, 等. 肺癌中NR4A3和CD133表达的临床意义及相关性[J]. 实用癌症杂志, 2015, 30(12): 1782-1785.DOI: 10.3969/j.issn.1001-5930.2015.12.008. [14] 杨伟玉, 刘驰, 谢辉, 等. miR-20a通过靶向NR4A3促进前列腺癌细胞增殖[J]. 中国生物化学与分子生物学报, 2021, 37(8): 1093-1099. DOI: 10.13865/j.cnki.cjbmb.2021.06.1629. [15] FEDOROVA O, PETUKHOV A, DAKS A, et al. Orphan receptor NR4A3 is a novel target of p53 that contributes to apoptosis[J]. Oncogene, 2019, 38(12): 2108-2122. DOI: 10.1038/s41388-018-0566-8. [16] WENZL K, TROPPAN K, NEUMEISTER P, et al. The nuclear orphan receptor NR4A1 and NR4A3 as tumor suppressors in hematologic neoplasms[J]. Current Drug Targets, 2015, 16(1): 38-46. DOI: 10.2174/1389450115666141120112818. [17] KASHYAP D, PAL D, SHARMA R, et al. Global increase in breast cancer incidence: risk factors and preventive measures[J]. BioMed Research International, 2022, 2022: 9605439. DOI: 10.1155/2022/9605439. [18] 中国抗癌协会肿瘤标志专业委员会乳腺癌标志物协作组. 基于靶标指导乳腺癌精准治疗标志物临床应用专家共识(2022版)[J]. 中国癌症防治杂志, 2022, 14(4): 346-362. DOI: 10.3969/j.issn.1674-5671.2022.04.01. [19] SUN L C, LIU M Q, SUN G C, et al. Notch signaling activation in cervical cancer cells induces cell growth arrest with the involvement of the nuclear receptor NR4A2[J]. Journal of Cancer, 2016, 7(11): 1388-1395. DOI: 10.7150/jca.15274. [20] IBNAT N, KAMARUZMAN N I, ASHAIE M, et al. Transfection with p21 and p53 tumor suppressor plasmids suppressed breast tumor growth in syngeneic mouse model[J]. Gene, 2019, 701: 32-40. DOI: 10.1016/j.gene.2019.02.082. [21] DUFFY M J, SYNNOTT N C, O'GRADY S, et al. Targeting p53 for the treatment of cancer[J]. Seminars in Cancer Biology, 2022, 79: 58-67. DOI: 10.1016/j.semcancer.2020.07.005. [22] BIEGING K T, MELLO S S, ATTARDI L D. Unravelling mechanisms of p53-mediated tumour suppression[J]. Nature Reviews Cancer, 2014, 14(5): 359-370. DOI: 10.1038/nrc3711. [23] HERRING J A, ELISON W S, TESSEM J S. Function of Nr4a orphan nuclear receptors in proliferation, apoptosis and fuel utilization across tissues[J]. Cells, 2019, 8(11): 1373. DOI: 10.3390/cells8111373. |
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