摘要
目的近年来,非肌肉肌浆球蛋白重链ⅡA(NMHCⅡA)在肿瘤细胞中的作用备受关注。笔者团队前期研究发现高表达的NMHCⅡA可以作为预示膀胱癌患者不良预后的分子标志物,但其在膀胱癌发生发展过程中的作用尚不清楚。方法采用实时荧光定量PCR和western blot分析膀胱癌细胞株中NMHCⅡA的表达情况,采用划痕实验检测细胞的迁移能力及Transwell侵袭实验检测细胞的侵袭能力。结果沉默内源性NMHCⅡA表达后能降低膀胱癌细胞侵袭及转移能力。结论 NMHCⅡA可促进膀胱癌细胞侵袭及转移能力。
Objective Non-muscle myosin heavy chain ⅡA(NMHC ⅡA)plays a significant role in tumor progression and metastasis.Our prior study showed that the expression of NMHC ⅡA was much higher in human bladder cancer sample than that in adjacent tissue.The increased level of NMHC ⅡA expression was correlated with worse prognosis.However,the role of NMHC ⅡA is unknown in the invasion and metastasis of bladder cancer.Methods RT-PCR and western blotting were used to examine NMHC ⅡA expression levels in normal bladder epithelial cells and bladder cancer cell lines.The migration and invasion ability of cells was tested by wound healing assay and Transwell invasion assay,respectively.Results Our study showed that knockdown of NMHC ⅡA inhibited migration and invasion in bladder cancer cell line.Conclusion The study indicated that NMHC ⅡA expression increased the invasion and metastasis ability of bladder cancer cell line in vitro.
引文
[1]CHEN W,ZHENG R,BAADE P,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66:115-132.
[2]TRENTA P,CALABRòF,CERBONE L,et al.Chemotherapy for muscle-invasive bladder cancer[J].Curr Treat Options Oncol,2016,17(1):6.
[3]WOLDU S L,BAGRODIA A,LOTAN Y.Guideline of guidelines:non-muscle-invasive bladder cancer[J].BJU Int,2017,119(3):371-380.
[4]VICENTE-MANZANARES M,MA X,ADELSTEIN R S,et al.Non-muscle myosinⅡtakes centre stage in cell adhesion and migration[J].Nat Rev Mol Cell Biol,2009,10(11):778-790.
[5]ARⅡJ,GOTO H,SUENAGA T,et al.Non-muscle myosinⅡA is a functional entry receptor for herpes simplex virus-1[J].Nature,2010,467(7317):859-862.
[6]SIMONS M,WANG M,MCBRIDE O,et al.Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes[J].Circ Res,1991,69(2):530-539.
[7]XIONG D,YE Y L,CHEN M K,et al.Non-muscle myosinⅡis an independent predictor of overall survival for cystectomy candidates with early-stage bladder cancer[J].Oncol Rep,2012,28(5):1625-1632.
[8]LIU D,ZHANG L,SHEN Z,et al.Clinicopathological Significance of NMⅡA Overexpression in Human Gastric Cancer[J].Int J Mol Sci,2012,13(11):15291-15304.
[9]MAEDA J,HIRANO T,OGIWARA A,et al.Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy[J].Br J Cancer,2008,98(3):596-603.
[10]KATONO K,SATO Y,JIANG S X,et al.Prognostic significance of MYH9expression in resected non-small cell lung cancer[J].PLoS One,2015,10(3):e0121460.
[11]DULYANINOVA N G,HOUSE R P,BETAPUDI V,et al.Myosin-ⅡA heavy-chain phosphorylation regulates the motility of MDA-MB-231carcinoma cells[J].Mol Biol Cell,2007,18(8):3144-3155.
[12]MEDJKANE S,PEREZ-SANCHEZ C,GAGGIOLI C,et al.Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis[J].Nat Cell Biol,2009,11(3):257-268.
[13]YE G,HUANG K,YU J,et al.MicroRNA-647Targets SRF-MYH9Axis to Suppress Invasion and Metastasis of Gastric Cancer[J].Theranostics,2017,7(13):3338-3353.
[14]FUJITA T,KITAURA F,FUJⅡH.A critical role of the Thy28-MYH9axis in B cell-specific expression of the Pax5gene in chicken B cells[J].PLoS One,2015,10(1):e0116579.
[15]ZHAO B,QI Z,LI Y,et al.The non-muscle-myosin-Ⅱheavy chain Myh9mediates colitis-induced epithelium injury by restricting Lgr5+stem cells[J].Nat Commun,2015,6:7166.