|Table of Contents|

The effect and mechanism of ZW10 interacting kinetochore protein on proliferation of neuroblastoma cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 01
Page:
43-50
Research Field:
Publishing date:

Info

Title:
The effect and mechanism of ZW10 interacting kinetochore protein on proliferation of neuroblastoma cells
Author(s):
YUAN Wen; CAI Qinzhen; WANG Jun; TUO Wenbin; XIANG Yun; YUAN Chunhui
Department of Laboratory Medicine,Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital),Tongji Medical College,Huazhong University of Science & Technology,Hubei Wuhan 430016,China.
Keywords:
neuroblastoma; ZWINT; MYCN amplification; proliferation; cell cycle
PACS:
R730.264
DOI:
10.3969/j.issn.1672-4992.2023.01.007
Abstract:
Objective:To investigate the effect of ZW10 interacting kinetochore protein (ZWINT) on neuroblastoma (NB) cell proliferation and its potential mechanism.Methods:GEO database was used to analyze the correlation of ZWINT with prognosis and different clinical stages in NB.ZWINT was interfered in MYCN amplified NB cell lines by shRNA,and cell proliferation was then evaluated by using EdU cell proliferation assay.Cell cycle distribution was detected by flow cytometry.The repair ability of DNA damage was detected by γH2AX immunofluorescence staining.The effect of interfering/overexpressing MYCN on ZWINT expression was analyzed by qRT-PCR and Western blot.The binding site of MYCN on ZWINT promoter was predicted by online database,and the effect of MYCN on ZWINT transcription was detected by ChIP-PCR and luciferase assay.To further validate the effects of ZWINT on MYCN-mediated cell proliferation,cycle and DNA damage repair,we examined Tet-on MYCN SH-SY-5Y cells with ZWINT knockdown.Results:High expression of ZWINT mRNA was related to significantly shorter overall and event-free survival for neuroblastoma patients.Moreover,increased ZWINT expression correlated significantly with advanced tumor stages.ZWINT silencing efficiently inhibited cellular proliferation,increased the percentage of cell population in G2/M phase,and increased the formation of γH2AX foci.ZWINT expression of MYCN-amplified was significantly higher than non-MYCNN-amplified NB tissues and cell lines.MYCN can bind to promoter and regulate ZWINT expression.Overexpression of MYCN significantly promoted SH-SY-5Y cells proliferation,and which could be blocked by simultaneously transfecting with shZWINT.Conclusion:ZWINT is a prognostic marker in NB,which was regulated by MYCN.Silencing ZWINT induced G2/M cell cycle arrest,and DNA damage repair increase,thereby inhibited the proliferation of MYCN-amplified NB cell.

References:

［1］HU XJ,ZHENG WS,ZHU QS,et al.Increase in DNA damage by MYCN knockdown through regulating nucleosome organization and chromatin state in neuroblastoma［J］.Front Genet,2019,10:684.
［2］KROESEN M,BLL C,GIELEN PR,et al.Anti-GD2 mAb and Vorinostat synergize in the treatment of neuroblastoma［J］.Oncoimmunology,2016,5(6):e1164919.
［3］FAESEN AC,THANASOULA M,MAFFINI S,et al.Basis of catalytic assembly of the mitotic checkpoint complex［J］.Nature,2017,542(7642):498-502.
［4］LI HN,ZHENG WH,DU YY,et al.ZW10 interacting kinetochore protein may serve as a prognostic biomarker for human breast cancer:An integrated bioinformatics analysis［J］.Oncol Lett,2020,19(3):2163-2174.
［5］YING HN,XU ZY,CHEN MM,et al.Overexpression of Zwint predicts poor prognosis and promotes the proliferation of hepatocellular carcinoma by regulating cell-cycle-related proteins［J］.Onco Targets Ther,2018,11:689-702.
［6］AKABANE S,OUE N,SEKINO Y,et al.KIFC1 regulates ZWINT to promote tumor progression and spheroid formation in colorectal cancer［J］.Pathol Intl,2021,71(7):441-452.
［7］TANG J,HE D,YANG PR,et al.Genome-wide expression profiling of glioblastoma using a large combined cohort［J］.Sci Rep,2018,8(1):15104.
［8］URBANUCCI A,SAHU B,SEPPL J,et al.Overexpression of androgen receptor enhances the binding of the receptor to the chromatin in prostate cancer［J］.Oncogene,2012,31(17):2153-2163.
［9］BINENIEK J,CHILDRESS C,SWATSKI MD,et al.COX-2 inhibitors arrest prostate cancer cell cycle progression by down-regulation of kinetochore/centromere proteins［J］.Prostate,2014,74(10):999-1011.
［10］YUAN W,XIE SP,WANG M,et al.Bioinformatic analysis of prognostic value of ZW10 interacting protein in lung cancer［J］.Onco Targets Ther,2018,11:1683-1695.
［11］YUAN W,XIE SP,LIU P,et al.Digital analysis of immunostaining of ZW10 interacting protein in human lung tissues［J］.J Vis Exp,2019,147:10.3791/58551.
［12］ZEID R,LAWLOR MA,POON E,et al.Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma［J］.Nat Genet,2018,50(4):515-523.
［13］XIANG T,YUAN CH,GUO X,et al.The novel ZEB1-upregulated protein PRTG induced by Helicobacter pylori infection promotes gastric carcinogenesis through the cGMP/PKG signaling pathway［J］.Cell Death & Disease,2021,12(2):150.
［14］XU ZZ,ZHOU Y,CAO YX,et al.Identification of candidate biomarkers and analysis of prognostic values in ovarian cancer by integrated bioinformatics analysis［J］.Med Oncol,2016,33(11):130.
［15］PENG F,LI Q,NIU SQ,et al.ZWINT is the next potential target for lung cancer therapy［J］.J Cancer Res Clin Oncol,2019,145(3):661-673.
［16］JOHNSEN JI,DYBERG C,FRANSSON S,et al.Molecular mechanisms and therapeutic targets in neuroblastoma［J］.Pharmacol Res,2018,131:164-176.
［17］BOBOILA S,LOPEZ G,YU J,et al.Transcription factor activating protein 4 is synthetically lethal and a master regulator of MYCN-amplified neuroblastoma［J］.Oncogene,2018,37(40):5451-5465.
［18］LIN T,ZHANG YZ,LIN ZM,et al.ZWINT is a promising therapeutic biomarker associated with the immune microenvironment of hepatocellular carcinoma［J］.Int J Gen Med,2021,14:7487-7501.
［19］MELAIU O,CHIERICI M,LUCARINI V,et al.Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma［J］.Nat Commun,2020,11(1):5992.
［20］徐伟立,时保军,李索林,等.靶向抑制髓系抑制性细胞调控肿瘤微环境对神经母细胞瘤荷瘤小鼠免疫疗效的影响［J］.中华小儿外科杂志,2020,41(09):846-854. XU WL,SHI BJ,LI SL,et al.Regulation of tumor microenvironment by targeted inhibiting of myeloid-derived suppressor cells for influencing immune efficacy of neuroblastoma-bearing mice［J］.Chin J Pediatr Surg,2020,41(09):846-854.

Memo

Memo:
湖北省卫健委科研项目（编号：WJ2021M016）;湖北省武汉市卫健委科研项目（编号：WX20C03，WX18Q03）
Last Update: 2022-11-30