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

doi:10.3870/j.issn.1672-0741.24.07.025

Abstract

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

CLC Number:

R734.2

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.

References

[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.

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

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