|Table of Contents|

SPAG6 promotes the proliferation,migration and invasion of ovarian cancer cells

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

Issue:
2023 05
Page:
811-817
Research Field:
Publishing date:

Info

Title:
SPAG6 promotes the proliferation,migration and invasion of ovarian cancer cells
Author(s):
LYU Linglu1; FU Guoqing1; HU Lian1; YUE Junqiu2; NIE Lei3; LI Wei4; ZHANG Zhibing1; 4; ZHANG Ling1
1.Department of Environmental Health and Occupational Medicine,School of Public Health,College of Medicine,Wuhan University of Science and Technology,Hubei Wuhan 430065,China;2.Department of Pathology;3.Department of Hepatobiliary and Pancreatic Surgery,Hubei Cancer Hospital,Hubei Wuhan 430079,China;4.Department of Obstetrics and Gynecology,Wayne State University,Detroit MI 48201,USA.
Keywords:
ovarian cancer; SKOV-3 cell; SPAG6; proliferation
PACS:
R737.31
DOI:
10.3969/j.issn.1672-4992.2023.05.005
Abstract:
Objective：To investigate the effect of sperm-associated antigen 6 (SAPG6) on the proliferation,invasion and migration of ovarian cancer cells.Methods:Normal ovarian epithelial cells (NOE-71) and ovarian cancer cells (SKOV-3,OVCAR-3) were cultured in vitro,and the expression of SPAG6 gene in the cells was detected by real-time fluorescent quantitative PCR (RT-qPCR) experiments.Four "SPAG6-shRNA" plasmids which potentially inhibit the expression of SPAG6 were transfected into ovarian cancer cells SKOV-3,and then we screened the stably transfected cell line with the SPAG6 expression effectively down-regulated by RT-qPCR and Western blot.The effect of SPAG6 silencing on the cell proliferation was analyzed by cell counting and colony formation assays.Moreover,the effect of SPAG6 knockdown on cell migration and invasion was examined by wound healing migration assay and Transwell invasion and migration assay.And the effect of SPAG6 knockdown on cell cycle was examined by flow cytometry.Immunofluorescence and Western blot was used to detect the influence of SPAG6 on the distribution of p27kip1 in SKOV-3 cells.Results:The expression of SPAG6 gene in ovarian cancer cells SKOV-3 and OVCAR-3 was significantly higher than that of normal ovarian epithelial cells NOE-71,and the expression was the strongest in SKOV-3 cells.RT-qPCR and Western blot experiment showed that two types of "SPAG6-shRNA" plasmids effectively inhibited the expression of SPAG6.Compared to the control,inhibition of SPAG6 expression could reduce the proliferation and colony formation rate of SKOV-3 cells,and the difference was statistically significant (P＜0.01).Wound healing migration and Transwell assays showed that silencing of SPAG6 expression could reduce the migration and invasion ability of SKOV-3 cells (P＜0.01).Flow cytometry showed that SPAG6 knockdown could significantly up-regulate cells in G0/G1 phase and down-regulate in S phase (P＜0.01).Inhibition of SPAG6 expression in SKOV-3 cells reduced the level of p27kip1 in the cytoplasm and increased its levels in the nucleus.Conclusion:SPAG6 promotes the proliferation,migration and invasion of ovarian cancer cells.

References:

［1］SIEGEL RL,MILLER KD,JEMAL A.Cancer statistics,2020［J］.CA Cancer J Clin,2020,70(1):7-30.
［2］马明月，吴瑾.上皮性卵巢癌预后因素的研究进展［J］.现代肿瘤医学，2020，28(17)：3085-3088. MA MY，WU J.Research progress on prognostic factors of epithelial ovarian cancer［J］.Modern Oncology，2020，28(17)：3085-3088.
［3］张丽滢，李力.分子进化理论在卵巢癌发生及多药耐药的研究进展［J］.中国肿瘤生物治疗杂志，2017，24(05)：553-557. ZHANG LY，LI L.Research progress of molecular evolution theory in the occurrence and multidrug resistance of ovarian cancer［J］.Chinese Journal of Cancer Biotherapy，2017，24(05)：553-557.
［4］LI X,WANG X.The emerging roles and therapeutic potential of exosomes in epithelial ovarian cancer［J］.Mol Cancer,2017,16(1):92.
［5］刘姗，王静，刘路，等.卵巢癌复发治疗的研究进展［J］.肿瘤药学，2019，9(02)：189-192. LIU S，WANG J，LIU L，et al.Research progress in the treatment of recurrence of ovarian cancer［J］.Oncology Pharmacy，2019，9(02)：189-192.
［6］褚雁鸿，刘芹，刘宝瑞.新抗原：开启肿瘤治疗性疫苗的新时代［J］.肿瘤综合治疗电子杂志，2018，4(02)：6-13. CHU YH，LIU Q，LIU BR.Neoantigens:Opening a new era of tumor therapeutic vaccines［J］.Electronic Journal of Comprehensive Cancer Treatment，2018，4(02)：6-13.
［7］SILINA K,ZAYAKIN P,KALNINA Z,et al.Sperm-associated antigens as targets for cancer immunotherapy:expression pattern and humoral immune response in cancer patients［J］.J Immunother,2011,34(1):28-44.
［8］COAN M,RAMPIONI VG,CESARATTO L,et al.Exploring the role of fallopian ciliated cells in the pathogenesis of high-grade serous ovarian cancer［J］.Int J Mol Sci,2018,19(9):2512.
［9］MENG X,SUN X,LIU Z,et al.A novel era of cancer/testis antigen in cancer immunotherapy［J］.Int Immunopharmacol,2021,98(98):107889.
［10］GORDEEVA O.Cancer-testis antigens:Unique cancer stem cell biomarkers and targets for cancer therapy［J］.Semin Cancer Biol,2018,53(53):75-89.
［11］LIN S,LYU Y,ZHENG L,et al.Expression and prognosis of sperm-associated antigen 1 in human breast cancer［J］.Onco Targets Ther,2021,14(14):2689-2698.
［12］BUECHLER S.Low expression of a few genes indicates good prognosis in estrogen receptor positive breast cancer［J］.BMC Cancer,2009,9(9):243.
［13］XIAO C,LI M,HUANG Q,et al.SPAG9 promotes prostate cancer proliferation and metastasis via MAPK signaling pathway［J］.Am J Transl Res,2019,11(8):5249-5260.
［14］NEILSON L,SCHNEIDER P,VAN DEERLIN P,et al.cDNA cloning and characterization of a human sperm antigen (SPAG6) with homology to the product of the Chlamydomonas PF16 locus［J］.Genomics,1999,60(3):272-280.
［15］ZHENG DF,WANG Q,WANG JP,et al.The emerging role of sperm-associated antigen 6 gene in the microtubule function of cells and cancer［J］.Mol Ther Oncolytics,2019,15(15):101-107.
［16］LI X,XU L,SUN G,et al.Spag6 mutant mice have defects in development and function of spiral ganglion neurons,apoptosis,and higher sensitivity to Paclitaxel［J］.Sci Rep,2017,7(1):8638.
［17］LIU Y,ZHANG L,LI W,et al.The sperm-associated antigen 6 interactome and its role in spermatogenesis［J］.Reproduction,2019,158(2):181-197.
［18］LIU G,CLARET FX,ZHOU F,et al.Jab1/COPS5 as a novel biomarker for diagnosis,prognosis,therapy prediction and therapeutic tools for human cancer［J］.Front Pharmacol,2018,9(9):135.
［19］HE W,WANG X,CHEN L,et al.A crosstalk imbalance between p27kip1and its interacting molecules enhances breast carcinogenesis［J］.Cancer Biother Radiopharm,2012,27(7):399-402.
［20］TOMODA K,KUBOTAU Y,ARATA Y,et al.The cytoplasmic shuttling and subsequent degradation of p27kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex［J］.J Biol Chem,2002,277(3):2302-2310.
［21］KITCHEN MO,BRYAN RT,HAWORTH KE,et al.Methylation of HOXA9 and ISL1 predicts patient outcome in high-grade non-invasive bladder cancer［J］.PLoS One,2015,10(9):e0137003.
［22］ZHANG R,ZHU H,YUAN Y,et al.SPAG6 promotes cell proliferation and inhibits apoptosis through the PTEN/PI3K/AKT pathway in Burkitt lymphoma［J］.Oncol Rep,2020,44(5):2021-2030.
［23］LI W,MUKHERJEE A,WU J,et al.Sperm associated antigen 6 (SPAG6) regulates fibroblast cell growth,morphology,migration and ciliogenesis［J］.Sci Rep,2015,5(5):16506.

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湖北省高等学校优秀中青年科技创新团队计划（编号：T2020003）；湖北省科技计划项目（编号：2018CFA040）；湖北省教育厅科学技术研究计划指导性项目（编号：B2020014）
Last Update: 2023-01-31