NRBP1在评估非小细胞肺癌患者预后中的价值及其调控G1/S期转变的相关机制*

doi:10.3870/j.issn.1672-0741.24.07.025

摘要/Abstract

摘要： 目的探讨核受体结合蛋白1(nuclear receptor-binding protein 1,NRBP1)评估非小细胞肺癌(non-small cell lung cancer,NSCLC)患者预后的价值并通过体外实验分析相关调控机制。方法纳入2015年1月至2017年12月在武汉市第三医院接受手术治疗的67例NSCLC患者,免疫组织化学检测NRBP1在NSCLC肿瘤和癌旁组织中的表达水平并分析其与临床病理参数间的关系;Kaplan-Meier plotter数据库分析NRBP1和NSCLC患者预后的相关性。以siRNA敲减NRBP1在A549和95D细胞中的表达,应用CCK-8法检测细胞增殖能力,细胞克隆实验检测克隆形成情况,流式细胞术分析细胞周期改变,qRT-PCR和Western blot分析NRBP1表达,Western blot分析A549细胞增殖与周期相关蛋白Ki-67,CDK4,Cyclin D1,P21的表达。结果与癌旁组织相比,NRBP1在NSCLC肺癌组织中表达阳性率增加(P＜0.01),其高表达与TNM分期相关(P＜0.05)。与NRBP1高表达组相比,NRBP1低表达组生存期更长[HR=1.28(1.13~1.44),Log-rank P＜0.01]。下调NRBP1在A549和95D细胞中的表达,可以抑制细胞增殖和克隆形成,G₁期细胞增加,S期减少,下调NRBP1在A549细胞表达可导致Ki-67,CDK4,cyclin D1表达减少,P21的表达增加。结论 NRBP1在NSCLC患者中的表达增加与患者预后不良相关,其可通过调节细胞周期G₁/S期转变,参与NSCLC细胞增殖的调控。

关键词: 核受体结合蛋白1, 非小细胞肺癌, 预后, 细胞周期

Abstract: Objective To explore the value of nuclear receptor-binding protein 1(NRBP1)in assessing the prognosis of non-small cell lung cancer(NSCLC)patients and analyze the related regulatory mechanisms through in vitro experiments. Methods Sixty-seven NSCLC patients who underwent surgical treatment at Wuhan Third Hospital from January 2015 to December 2017 were included.Immunohistochemical analysis was performed to assess NRBP1 expression in NSCLC tumor tissues and adjacent tissues.Its correlation with clinicopathological parameters was analyzed.Additionally,the Kaplan-Meier plotter database was used to evaluate the association between NRBP1 and the prognosis of NSCLC patients.SiRNA-mediated knockdown of NRBP1 expression in A549 and 95D cells was performed,and cell proliferation ability was detected via a CCK-8 assay.Cell colony formation experiments were performed to investigate the effects on colony formation.Flow cytometry was used to analyze changes in the cell cycle.qRT-PCR and Western blotting were employed to analyze NRBP1 expression.The expression of Ki-67,CDK4,cyclin D1,and P21,which are related to cell proliferation and the cell cycle in A549 cells,was detected in A549 cells via Western blotting. Results Compared with that in adjacent tissues,the positive expression rate of NRBP1 in NSCLC lung cancer tissue was greater(P<0.01),which was correlated with TNM stage(P<0.05).Compared with patients with high NRBP1 expression,patients with low NRBP1 expression had longer overall survival[HR=1.28(1.13-1.44),log-rank P<0.01].Downregulation of NRBP1 expression in A549 cells and 95D cells inhibited cell proliferation and colony formation,increasing the number of cells in the G₁ phase and decreasing the number of cells in the S phase.Downregulation of NRBP1 expression in A549 cells led to decreases in Ki-67,CDK4,and cyclin D1 expression and an increase in P21 expression. Conclusion Increased expression of NRBP1 in NSCLC is associated with poor prognosis,and NRBP1 can participate in the regulation of NSCLC cell proliferation by altering the G₁/S phase of the cell cycle.

Key words: NRBP1, non-small cell lung cancer, prognosis, cell cycle

中图分类号:

R734.2

徐建群, 黄波, 郭红荣, 周利君, 程津津, 方思, 张娣, 何成成, 陈天佑. NRBP1在评估非小细胞肺癌患者预后中的价值及其调控G₁/S期转变的相关机制^*[J]. 华中科技大学学报（医学版）, 2026, 55(1): 27-33.

Xu Jianqun, Huang Bo, Guo Hongrong et al. Value of NRBP1 in Assessing Prognosis of Non-Small Cell Lung Cancer Patients and Its Correlation with G₁/S Regulatory Mechanism[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(1): 27-33.

参考文献

[1] Alessi J V,Elkrief A,Ricciuti B,et al.Clinicopathologic and genomic factors impacting efficacy of first-line chemoimmunotherapy in advanced NSCLC[J].J Thorac Oncol,2023,18(6):731-743.
[2] Zhang Y,Hu J,Ji K,et al.CD39 inhibition and VISTA blockade may overcome radiotherapy resistance by targeting exhausted CD8⁺T cells and immunosuppressive myeloid cells[J].Cell Rep Med,2023,4(8):101151-101167.
[3] Chen P,Liu Y,Wen Y,et al.Non-small cell lung cancer in China[J].Cancer Commun(Lond),2022,42(10):937-970.
[4] Wu J,Lin Z.Non-small cell lung cancer targeted therapy:Drugs and mechanisms of drug resistance[J].Int J Mol Sci,2022,23(23):15056-15073.
[5] Cascone T,Fradette J,Pradhan M,et al.Tumor immunology and immunotherapy of non-small-cell lung cancer[J].Cold Spring Harb Perspect Med,2022,12(5):a037895-a037909.
[6] Johnson M,Garassino M C,Mok T,et al.Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors:Focus on novel therapies[J].Lung Cancer,2022,170(2):41-51.
[7] Zhou Z,Ding Z,Yuan J,et al.Homologous recombination deficiency(HRD)can predict the therapeutic outcomes of immuno-neoadjuvant therapy in NSCLC patients[J].J Hematol Oncol,2022,15(1):62-78.
[8] Cheong M C,Wang Z,Jaleta T G,et al.Identification of a nuclear receptor/coactivator developmental signaling pathway in the nematode parasite strongyloides stercoralis[J].Proc Natl Acad Sci U S A,2021,118(8):e2021864118.
[9] Zhang Q,Fang H,Zhu Z.NRBP1 modulates uric acid transporter ABCG2 expression by activating the Wnt/β-catenin pathway in HK-2 cells[J].Nefrologia(Engl Ed),2023,43(2):204-212.
[10] Wu Q,Zhou X,Li P,et al.High NRBP1 expression promotes proliferation and correlates with poor prognosis in bladder cancer[J].J Cancer,2019,10(18):4270-4277.
[11] Li M,Jiang H,Chen S,et al.GATA binding protein 1 recruits histone deacetylase 2 to the promoter region of nuclear receptor binding protein 2 to affect the tumor microenvironment and malignancy of thyroid carcinoma[J].Bioengineered,2022,13(4):11320-11341.
[12] Liao Y,Yang Z,Huang J,et al.Nuclear receptor binding protein 1 correlates with better prognosis and induces caspase-dependent intrinsic apoptosis through the JNK signalling pathway in colorectal cancer[J].Cell Death Dis,2018,9(4):436-449.
[13] Hwang J,Haque M A,Suzuki H,et al.THG-1 suppresses SALL4 degradation to induce stemness genes and tumorsphere formation through antagonizing NRBP1 in squamous cell carcinoma cells[J].Biochem Biophys Res Commun,2020,523(2):307-314.
[14] Qin L,Sun X,Zhou F,et al.CircLRP6 contributes to prostate cancer growth and metastasis by binding to miR-330-5p to up-regulate NRBP1[J].World J Surg Oncol,2021;19(1):184.
[15] Tong H,Sun J,Fang J,et al.A machine learning model based on PET/CT radiomics and clinical characteristics predicts tumor immune profiles in non-small cell lung cancer:A retrospective multicohort study[J].Front Immunol,2022,13(8):859323-859335.
[16] Deng H,Liu J,Cai X,et al.Radical minimally invasive surgery after immuno-chemotherapy in initially-unresectable stage Ⅱ-IB non-small cell lung cancer[J].Ann Surg,2022,275(3):e600-e602.
[17] Yao W,Cao Q,Luo S,et al.Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of(R)-ketamine[J].Mol Psychiatry,2022,27(3):1618-1629.
[18] Yang X,Cruz M I,Nguyen E V,et al.The pseudokinase NRBP1 activates Rac1/Cdc42 via P-Rex1 to drive oncogenic signalling in triple-negative breast cancer[J].Oncogene,2023,42(11):833-847.
[19] Liao Y,Yang Z,Huang J,et al.Nuclear receptor binding protein 1 correlates with better prognosis and induces caspase-dependent intrinsic apoptosis through the JNK signalling pathway in colorectal cancer[J].Cell Death Dis,2018,9(4):436-447.
[20] Suski J M,Braun M,Strmiska V,et al.Targeting cell-cycle m-achinery in cancer[J].Cancer Cell,2021,39(6):759-778.
[21] Knudsen E S,Kumarasamy V,Nambiar R,et al.CDK/cyclin dependencies define extreme cancer cell-cycle heterogeneity and collateral vulnerabilities[J].Cell Rep,2022,38(9):110448-110462.
[22] Wang J,Su W,Zhang T,et al.Aberrant Cyclin D1 splicing in cancer:from molecular mechanism to therapeutic modulation[J].Cell Death Dis,2023,14(4):244-258.
[23] Qian Y,Li Y,Chen K,et al.Pan-cancer transcriptomic analysis identifies PLK1 crucial for the tumorigenesis of clearcell renal cell carcinoma[J].J Inflamm Res,2022,15(6):1099-1116.
[24] 孔德光,杨艳,余维巍.lncRNA MALAT1调控GPx3去甲基化参与非小细胞肺癌的发生发展[J].华中科技大学学报:医学版,2024,53(5):569-577.
Kong D G,Yang Y,Yu W W.lncRNA MALAT1 regulates GPx3 demethylation and is involved in the occurrence and development of non-small cell lung cancer[J].Acta Med Univ Sci Technol Huzhong,2024,53(5):569-577.
[25] An Y,Zhao J.Functionalized selenium nanotherapeutics synergizes with zoledronic acid to suppress prostate cancer cell growth through induction of mitochondria-mediated apoptosis and cell cycle S phase arrest[J].Front Oncol,2021,11(10):685784-685802.
[26] Churiyah C,Ningsih S,Firdayani F.The cytotoxic,apoptotic induction,and cell cycle arrest activities of solanum nigrum L.ethanolic extract on MCF-7 human breast cancer cell[J].Asian Pac J Cancer Prev,2020,21(12):3735-3741.
[27] Klein M E,Kovatcheva M,Davis L E,et al.CDK4/6 inhibitors:The mechanism of action may not be as simple as once thought[J].Cancer Cell,2018,34(1):9-20.

NRBP1在评估非小细胞肺癌患者预后中的价值及其调控G₁/S期转变的相关机制^*

Value of NRBP1 in Assessing Prognosis of Non-Small Cell Lung Cancer Patients and Its Correlation with G₁/S Regulatory Mechanism

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	黄丽云, 覃柳宇, 蒋运, 牛晓辉, 杨健叶, 龚静. 乳腺癌可选择性多聚腺苷酸化及其相关因素系统分析^*[J]. 华中科技大学学报（医学版）, 2026, 55(1): 34-44.
[2]	许腊梅, 凌锐, 汤翔, 陈伟豪, 孙康△ , 徐岷. 半胱氨酸蛋白酶抑制剂2在结直肠癌中的表达及其与患者预后的相关性分析[J]. 华中科技大学学报（医学版）, 2025, 54(6): 835-841.
[3]	丘楠, 任宇虹, 刘加夫, 林清华. 葫芦素B通过NAMPT-FoxO3a轴调控线粒体依赖性凋亡影响非小细胞肺癌细胞生物学行为[J]. 华中科技大学学报（医学版）, 2025, 54(5): 626-634.
[4]	程欢欢, 魏亚君, 刘立茹, 李志峰, 栾艳超. 程欢欢, 魏亚君, 刘立茹, 李志峰, 栾艳超[J]. 华中科技大学学报（医学版）, 2025, 54(5): 635-644.
[5]	武晓白, 向敏, 郭若楠, 王韵, 蒋一凡, 周月鹏, 舒扬. ATIC通过p21/p-Rb途径调控细胞周期相关蛋白促进胶质瘤细胞增殖[J]. 华中科技大学学报（医学版）, 2025, 54(5): 656-664.
[6]	郭若楠, 向敏, 武晓白, 王韵, 蒋一凡, 周月鹏, 舒扬. KCNJ14在神经胶质瘤细胞中的表达及其对细胞增殖的影响[J]. 华中科技大学学报（医学版）, 2025, 54(5): 665-671.
[7]	曹金俊, 黄河玉, 沙月娇, 蒋永新, 王超, 段萍萍, 李华君, 夏昊. 肺炎克雷伯菌血流感染患儿碳青霉烯类耐药的临床特征及预后危险因素分析[J]. 华中科技大学学报（医学版）, 2025, 54(5): 694-701.
[8]	张福全, 曹津铭, 吴雪杰. 血清miR-196b-5p和miR-199a-3p水平对非小细胞肺癌的诊断价值[J]. 华中科技大学学报（医学版）, 2025, 54(5): 702-709.
[9]	吕玉婉, 王季石. 不同年龄成人急性髓系白血病T淋巴细胞亚群免疫状态特点及与预后的关系[J]. 华中科技大学学报（医学版）, 2025, 54(4): 571-578.
[10]	朱江, 宋冬惠, 杨学明, 吴森斌. LysoPC、Tau与GDF-10在口腔鳞状细胞癌中的表达水平及预后相关性分析[J]. 华中科技大学学报（医学版）, 2025, 54(1): 90-94.
[11]	孔德光, 杨艳, 余维巍. lncRNA MALAT1调控GPx3去甲基化参与非小细胞肺癌的发生发展[J]. 华中科技大学学报（医学版）, 2024, 53(5): 569-577.
[12]	柳新胜, 江旺祥. 훸构建出血性卒中不良预后的风险预测模型:一项横断面研究[J]. 华中科技大学学报（医学版）, 2024, 53(3): 368-374.
[13]	张国薇, 周婷, 李连凤, 卢芳菲, 孔宪荣, 秦灵芝, 廖伟. Shh蛋白水平与肺腺癌临床特征及预后的关系[J]. 华中科技大学学报（医学版）, 2024, 53(2): 220-228.
[14]	焦一帆, 王昊, 刘宇辰, 谷振阳, 温亚男, 王莉莉, 窦立萍. STAT4在急性髓系白血病患者中的表达特征及其临床意义[J]. 华中科技大学学报（医学版）, 2023, 52(6): 781-790.
[15]	曾令成, 厉华, 陈如东, 杨洪宽, 陈坚, 于加省 . 无症状脑膜瘤的临床特征及手术治疗[J]. 华中科技大学学报（医学版）, 2023, 52(6): 847-854.