|Table of Contents|

The role and mechanism of ASPM in regulating cell cycle and inhibiting cell proliferation of nasopharyngeal carcinoma

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

Issue:
2023 08
Page:
1440-1447
Research Field:
Publishing date:

Info

Title:
The role and mechanism of ASPM in regulating cell cycle and inhibiting cell proliferation of nasopharyngeal carcinoma
Author(s):
YANG Kaiyan1; 2; QIN Qicai2; LI Xuxiang3; FENG Dayi3; NONG Fengjing2; YANG Qiuyun2; TANG Fengzhu1; QU Shenhong1
1.Department of Otorhinolaryngology,Head and Neck,People's Hospital of Guangxi Zhuang Autonomous Region,Guangxi Nanning 530000,China;2.Department of Otorhinolaryngology,Head and Neck Surgery;3.Department of Pathology,People's Hospital of Baise,Guangxi Baise 533000,China.
Keywords:
nasopharyngeal carcinoma; ASPM; enrichment analysis; cell cycle; cell proliferation
PACS:
R739.63
DOI:
10.3969/j.issn.1672-4992.2023.08.010
Abstract:
Objective:To explore the molecular function and mechanism of abnormal spindle-like microcephaly-associated protein (ASPM) in nasopharyngeal carcinoma by means of bioinformatics analysis,and to preliminarily verify the role of ASPM in nasopharyngeal carcinoma through cell experiments.Methods:Using the limma package of R language to analyze the gene differential expression of the nasopharyngeal carcinoma microarray data set.Using the clusterProfiler package of R language to conduct the enrichment analysis of ASPM-related genes.Flow cytometry,CCK8 experiment,real-time quantitative PCR and Western blotting and other methods were used to study the effect of silencing ASPM expression on the cycle and cell proliferation of nasopharyngeal carcinoma cells.Results:Differential expression analysis found that ASPM mRNA level was highly expressed in the nasopharyngeal carcinoma dataset (P＜0.001).Gene enrichment analysis found that ASPM-related genes were associated with cell cycle,DNA replication and other signaling pathways in nasopharyngeal carcinoma.The cell function experiments found that the nasopharyngeal cancer cell cycle was arrested in the G1 phase,and the proliferation of nasopharyngeal cancer cells was reduced by silencing the expression of ASPM.Silencing the expression of ASPM can affect the expression of nasopharyngeal carcinoma cell cycle and proliferation markers.Conclusion:ASPM may lead to tumorigenesis and progression by regulating signal pathways such as the cycle and DNA replication of nasopharyngeal carcinoma cells.Silencing the expression of ASPM mRNA in nasopharyngeal carcinoma cells can arrest the cell cycle in G1 phase and reduce cell proliferation.ASPM may serve as a potential target for improving prognosis of nasopharyngeal carcinoma.

References:

［1］ CHAN JY.Surgical management of recurrent nasopharyngeal carcinoma［J］.Oral Oncol,2014,50(10):913-917.
［2］ CHEN YP,CHAN A,LE QT,et al.Nasopharyngeal carcinoma［J］.Lancet,2019,394(10192):64-80.
［3］ KOUPRINA N,PAVLICEK A,COLLINS NK,et al.The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein［J］.Hum Mol Genet,2005,14(15):2155-2165.
［4］ PAI VC,HSU CC,CHAN TS,et al.ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3-β-catenin signaling［J］.Oncogene,2019,38(8):1340-1353.
［5］ WANG J,LIANG J,LI H,et al.Oncogenic role of abnormal spindle-like microcephaly-associated protein in lung adenocarcinoma［J］.Int J Oncol,2021,58(5):23.
［6］ GAUTIER L,COPE L,BOLSTAD BM,et al.affy-analysis of Affymetrix GeneChip data at the probe level［J］.Bioinformatics,2004,20(3):307-315.
［7］ LEEK JT,JOHNSON WE,PARKER HS,et al.The sva package for removing batch effects and other unwanted variation in high-throughput experiments［J］.Bioinformatics,2012,28(6):882-883.
［8］ Gene Ontology Consortium.The Gene Ontology resource:enriching a Gold mine［J］.Nucleic Acids Res,2021,49(D1):D325-D334.
［9］ KANEHISA M,SATO Y,FURUMICHI M,et al.New approach for understanding genome variations in KEGG［J］.Nucleic Acids Res,2019,47(D1):D590-D595.
［10］ SUBRAMANIAN A,TAMAYO P,MOOTHA VK,et al.Gene set enrichment analysis:a knowledge-based approach for interpreting genome-wide expression profiles［J］.Proc Natl Acad Sci USA,2005,102(43):15545-15550.
［11］ YU G,WANG LG,HAN Y,et al.clusterProfiler:an R package for comparing biological themes among gene clusters［J］.OMICS,2012,16(5):284-287.
［12］ 安晓静.ASPM在结肠腺癌中的表达及与Wnt信号通路相关性的研究［D］.北京:中国人民解放军医学院,2019. AN XJ.Expression of ASPM in colon adenocarcinoma and its correlation with Wnt signaling pathway［D］.Beijing:Chinese People's Liberation Army Medical College,2019.
［13］ DENG T,LIU Y,ZHUANG J,et al.ASPM is a prognostic biomarker and correlates with immune infiltration in kidney renal clear cell carcinoma and liver hepatocellular carcinoma［J］.Front Oncol,2022,12:632042.
［14］ HSU CC,LIAO WY,CHANG KY,et al.A multi-mode Wnt- and stemness-regulatory module dictated by FOXM1 and ASPM isoform I in gastric cancer［J］.Gastric Cancer,2021,24(3):624-639.
［15］ TIAN X,WANG N.Upregulation of ASPM,BUB1B and SPDL1 in tumor tissues predicts poor survival in patients with pancreatic ductal adenocarcinoma［J］.Oncol Lett,2020,19(4):3307-3315.
［16］ WU Y,YOU Y,CHEN L,et al.Abnormal spindle-like microcephaly-associated protein promotes proliferation by regulating cell cycle in epithelial ovarian cancer［J］.Gland Surg,2022,11(4):687-701.
［17］ FISH JL,KOSODO Y,ENARD W,et al.Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells［J］.Proc Natl Acad Sci USA,2006,103(27):10438-10443.
［18］ HIGGINS J,MIDGLEY C,BERGH AM,et al.Human ASPM participates in spindle organisation,spindle orientation and cytokinesis［J］.BMC Cell Biol,2010,11:85.
［19］ ZHONG X,LIU L,ZHAO A,et al.The abnormal spindle-like,microcephaly-associated (ASPM) gene encodes a centrosomalprotein［J］.Cell Cycle,2005,4(9):1227-1229.
［20］ CAPECCHI MR,POZNER A.ASPM regulates symmetric stem cell division by tuning Cyclin E ubiquitination［J］.Nat Commun,2015,6:8763.
［21］ PEREZDE CASTRO I,DECARCER G,MALUMBRES M.A census of mitotic cancer genes:new insights into tumor cell biology and cancer therapy［J］.Carcinogenesis,2007,28(5):899-912.
［22］ 贾未玲,于淼.CyclinB1与肿瘤细胞周期调控［J］.哈尔滨商业大学学报（自然科学版）,2016,32(6):659-662. JIA WL,YU M.CyclinB1 and tumor cell cycle regulation［J］.Journal of Harbin University of Commerce (Natural Science Edition),2016,32(6):659-662.
［23］ LEW DJ,BURKE DJ.The spindle assembly and spindle position checkpoints［J］.Annu Rev Genet,2003,37:251-282.
［24］ KOMATSU M,YOSHIMARU T,MATSUO T,et al.Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis［J］.Int J Oncol,2013,42(2):478-506.
［25］ CHEN X,HUANG L,YANG Y,et al.ASPM promotes glioblastoma growth by regulating G1 restriction point progression and Wnt-β-catenin signaling［J］.Aging (Albany NY),2020,12(1):224-241.
［26］ YUAN YJ,SUN Y,GAO R,et al.Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of lung squamous cell carcinoma (LSCC) by regulating CDK4［J］.J Cancer,2020,11(18):5413-5423.
［27］ WU Y,YOU Y,CHEN L,et al.Abnormal spindle-like microcephaly-associated protein promotes proliferation by regulating cell cycle in epithelial ovarian cancer［J］.Gland Surg,2022,11(4):687-701.
［28］ GAO ZY,YU F,JIA HX,et al.ASPM predicts poor prognosis and regulates cell proliferation in bladder cancer［J］.Kaohsiung J Med Sci,2020,36(12):1021-1029.
［29］ YANG Q,QI M,CHEN Y,et al.ASPM is a novel candidate gene associated with colorectal cancer cell growth［J］.DNA Cell Biol,2021,40(7):921-935.
［30］ KITAO H,IIMORI M,KATAOKA Y,et al.DNA replication stress and cancer chemotherapy［J］.Cancer Sci,2018,109(2):264-271.
［31］ YAO G.Modelling mammalian cellular quiescence［J］.Interface Focus,2014,4(3):20130074.
［32］ CHAMPERIS TSANIRAS S,KANELLAKIS N,SYMEONIDOU IE,et al.Licensing of DNA replication,cancer,pluripotency and differentiation:an interlinked world［J］.Semin Cell Dev Biol,2014,30:174-180.
［33］ WANG C,CHE J,JIANG Y,et al.CDT1 facilitates metastasis in prostate cancer and correlates with cell cycle regulation［J］.Cancer Biomark,2022,34(3):459-469.
［34］ MUGHAL MJ,MAHADEVAPPA R,KWOK HF.DNA replication licensing proteins:Saints and sinners in cancer［J］.Semin Cancer Biol,2019,58:11-21.
［35］ GONG S,QU X,YANG S,et al.RFC3 induces epithelial-mesenchymal transition in lung adenocarcinoma cells through the Wnt/β-catenin pathway and possesses prognostic value in lung adenocarcinoma［J］.Int J Mol Med,2019,44(6):2276-2288.

Memo

Memo:
National Natural Science Foundation of China(No.82060190);国家自然科学基金资助项目（编号：82060190）;广西卫健委科研课题（编号：Z20211109）；广西科技基地和人才专项（编号：桂科AD20297069）
Last Update: 1900-01-01