Effect of siRNA mediated FoxM1 silencing on proliferation and migration of nasopharyngeal carcinoma 5-8F cells <italic style="font-style: italic">via</italic> Wnt/β-catenin signaling pathway

您当前的位置：

首页 >

文章列表页 >

Effect of siRNA mediated FoxM1 silencing on proliferation and migration of nasopharyngeal carcinoma 5-8F cells via Wnt/β-catenin signaling pathway

Basic Medicine | 更新时间：2026-01-09

- Effect of siRNA mediated FoxM1 silencing on proliferation and migration of nasopharyngeal carcinoma 5-8F cells via Wnt/β-catenin signaling pathway
- Journal of Third Military Medical University Vol. 40, Issue 5, Pages: 380-386, 414(2018)
- 作者机构：
  
  1.400016 重庆，重庆医科大学附属第一医院耳鼻喉科
  2.646000 四川泸州，西南医科大学附属医院耳鼻咽喉头颈外科
  3.400016 重庆，重庆医科大学附属第一医院胸心外科
- 作者简介：
- 基金信息：
  
  the National Clinical Key-discipline Construction Program of China(〔2012〕649)
- DOI：10.16016/j.1000-5404.201709189
  CLC： R394.3;R730.23;R739.63
- Received：24 September 2017，
  
  Revised：2017-11-06，
  
  Published：15 March 2018
- 稿件说明：
移动端阅览
Jie WAN, Lin ZHU, Yue LEI, et al. Effect of siRNA mediated FoxM1 silencing on proliferation and migration of nasopharyngeal carcinoma 5-8F cells via Wnt/β-catenin signaling pathway[J]. Journal of Third Military Medical University, 2018, 40(5): 380-386, 414.
DOI：

Jie WAN, Lin ZHU, Yue LEI, et al. Effect of siRNA mediated FoxM1 silencing on proliferation and migration of nasopharyngeal carcinoma 5-8F cells via Wnt/β-catenin signaling pathway[J]. Journal of Third Military Medical University, 2018, 40(5): 380-386, 414. DOI： 10.16016/j.1000-5404.201709189.

摘要

目的

2

探讨FoxM1对鼻咽癌细胞5-8F恶性生物学行为的影响及其可能机制。

方法

2

将化学合成的靶向FoxM1的siRNA转染鼻咽癌细胞5-8F(FoxM1-siRNA组)，并设立空白对照组、阴性对照组，采用RT-PCR及Western blot检测FoxM1表达变化。采用MTT法、FCM法、Transwell法分别检测下调FoxM1表达对细胞增殖、周期、凋亡、迁移的影响。Western blot检测下调FoxM1表达后β-catenin、C-Myc、Cyclin D1、MMP-2、MMP-9蛋白表达变化。

结果

2

转染FoxM1-siRNA的5-8F细胞FoxM1 mRNA和蛋白表达水平降低(

P

＜0.05)。下调FoxM1表达可抑制5-8F细胞增殖(

P

＜0.05)，FoxM1-siRNA组的凋亡率为(22.68±0.67)%，较阴性对照组[(11.74±1.36)%

]

和空白对照组[(10.94±1.52)%

]

显著增加(

P

＜0.05)，细胞周期阻滞于G

0

/G

1

期。FoxM1-siRNA组细胞穿膜数(100.00±10.97)明显低于阴性对照组(246.00±6.66)和空白对照组(233.70±12.41)，细胞迁移能力降低(

P

＜0.05)。下调FoxM1的表达可抑制β-catenin细胞核表达，抑制C-Myc、Cyclin D1、MMP-2、MMP-9总蛋白表达(

P

＜0.001)。

结论

2

FoxM1表达下调抑制鼻咽癌细胞5-8F的增殖，诱导细胞凋亡，降低细胞迁移能力，使细胞周期阻滞于G

0

/G

1

期。其机制可能是通过抑制Wnt通路关键蛋白β-catenin细胞核表达从而抑制Wnt通路活性实现的。

Abstract

Objective

2

To investigate the effect of siRNA mediated FoxM1 silencing on malignant behaviors of nasopharyngeal carcinoma cell line 5-8F

via

Wnt/β-catenin signaling pathway.

Methods

2

The FoxM1-siRNA by chemical synthesis was transfected into 5-8F cells

and the blank and negative control cells were set up. Real-time PCR (RT-PCR) and Western blotting were used to detect the mRNA and protein levels of FoxM1 respectively. MTT assay

flow cytometry and Transwell chamber test were used to determine the effect of FoxM1 on proliferation

apoptosis

cell cycle distribution and migration of 5-8F cells. The protein expression levels of β-catenin

C-Myc

Cyclin D1

MMP-2 and MMP-9 were detected by Western blotting.

Results

2

The mRNA and protein levels of FoxM1 were decreased obviously after FoxM1-siRNA transfection in 5-8F cells (

P

<

0.05). When compared with the blank and negative control cells

the silence also inhibited the proliferation (

P

<

0.05)

but enhanced apoptotic rate [(22.68±0.67)%

vs

(10.94±1.52)% and (11.74±1.36)%

P

<

0.05

]

arrested the cell cycle at G

0

/G

1

phase

and decreased the number of invaded cells (100.00±10.97

vs

233.70±12.41 and 246.00±6.66) and cell migration ability (

P

<

0.05). Furthermore

Western blotting demonstrated that the nuclear protein level of β-catenin and the total protein levels of C-Myc

Cyclin D1

MMP-2 and MMP-9 were decreased after FoxM1-siRNA transfection (

P

<

0.05).

Conclusion

2

siRNA mediated FoxM1 silencing increases the apoptotic rate

inhibits the proliferation

reduces the migration

and arrests cell cycle at G

0

/G

1

phase in nasopharyngeal carcinoma 5-8F cells. Its mechanism may be through suppressing the expression of β-catenin

key protein of Wnt signaling pathway

and thus inhibiting the activation of the pathway.

关键词

Keywords

references

JIA W H, HUANG Q H, LIAO J, et al .Trends in incidence and mort ality of nasopharyngeal carcinoma over a 20-25 year period (1978/1983-2002) in Sihui and Cangwu counties in Southern China[J ] . BMC Cancer, 2006, 6:178.DOI: 10.1186/1471-2407-6-178.

LEE A W, SZE W M, AUJ S, et al . Treatment results for nasopharyngeal carcinoma in the modern era:the Hong Kong experience[J ] . Int J Radiat Oncol Biol Phys, 2005, 61(4):1107-1116.DOI:10.1016/j.ijrobp.2004.07.702.

LAOUKILI J, STAHL M, MEDEMA R H, et al . FoxM1: at the crossroads of ageing and cancer[J ] . Biochim Biophys Acta, 2007, 1775(1):92-102.DOI:10.1016/j.bbcan.2006.08.006.

BELLA L, ZONA S, NESTAL DE MORAESG, et al .FOXM1: A key oncofoetal transcription factor in health and disease[J ] . Semin Cancer Biol, 2014, 29: 32-39.DOI:10.1016/j.semcancer.2014.07.008.

GENTLES A J, NEWMAN A M, LIU C L, et al .The prognostic landscape of genes and infiltrating immune cells across human cancers[J ] . Nat Med, 2015, 21(8):938-945.DOI: 10.1038/nm.3909.

ACEBRON S P, KARAULANOV E, BERGER B S, et al . Mitotic Wnt signaling promotes protein stabilization and regulates cell size[J ] . Mol Cel l, 2014, 54(4):663-674.DOI:10.1016/j.molcel.2014.04.014.

ZHANG N, WEI P, GONG A, et al .FoxM1 promotes beta-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis[J ] . Cancer Cell, 2011, 20(4):427-442.DOI: 10.1016/j.ccr.2011.08.016.

江黎珠, 王棚, 陈鸿雁.FoxM1和COX-2在鼻咽癌组织中的表达及临床意义[J].第二军医大学学报, 2013, 34(6):645-649.DOI:10.3724/SP.J.1008.2013.00645.

JIANG L L, WANG P, CHEN HY.Expression of FoxM1 COX-2 in nasopharyngeal carcinoma tissues and the related clinical singnificance[J]. Acad J Second Mil Med Univ, 2013, 34(6):645-649.DOI:10.3724/SP.J.1008.2013.00645.

JIANG L, WANG P, CHEN L, et al . Down-regulation of FoxM1 by thiostrepton or small interfering RNA inhibits prolife-ration, transformation ability and angiogenesis, and induces apoptosis of nasopharyngeal carcinoma cells[J ] . Int J Clin Exp Pathol, 2014, 7(9):5450-5460.

LUO X, YAO J, NIE P, et al .FOXM1 promotes invasion and migration of colorectal cancer cells partially dependent on HSPA5 transactivation[J ] . Oncotarget, 2016, 7(18):26480-26495. DOI:10.18632/oncotarget.8419.

HALASI M, GARTEL A L.FOX(M1) news—it is cancer[J]. Mol Cancer Ther, 2013, 12(3):245-254. DOI:10.1158/1535-7163.mct-12-0712.

SONGX, FIATI KENSTON S S, ZHAO J, et al .Roles of FoxM1 in cell regulation and breast cancer targeting therapy[J ] . Med Oncol, 2017, 34(3):41.DOI:10.1007/s12032-017-0888-3.

WEI Y, SUN Q, ZHAOL, et al .LncRNA UCA1-miR-507-FOXM1 axis is involved in cell proliferation, invasion and G 0 /G 1 cell cycle arrestin melanoma[J ] . Med Oncol, 2016, 33(8):88.DOI:10.1007/s12032-016-0804-2..

BARGER C J, ZHANG W, HILLMANJ, et al .Genetic determinants of FOXM1 overexpression in epithelial ovarian cancer and functional contribution to cell cycle progression[J ] . Oncotarget, 2015, 6(29):27613-27627. DOI: 10.18632/oncotarget.4546.

刘亚男, 祝琳, 文韬宇, 等.叉头结构域抑制物6(FDI-6)通过下调细胞核FoxM1增加喉癌细胞凋亡并抑制其侵袭和迁移[J].细胞与分子免疫学杂志, 2017, 33(5):611-616.

LIU Y N, ZHU L, WEN T Y, et al .Forkhead domain inhibitor-6(FDI-6)increases apoptosis and inhibits invasion and migration of laryngeal carcinoma cells by down-regulating nuclear FoxM1[J ] . Chin J Cell Mol Immunol, 2017, 33(5):611-616.

HAMURCUZ, ASHOUR A, KAHRAMANN, et al .FOXM1 regulates expression of eukaryotic elongation factor 2 kinase and promotes proliferation, invasion and tumorogenesis of human triple negative breast cancer cells[J ] . Oncotarget, 2016, 7:16619-16635.DOI:10.18632/oncotarget.7672.

FENG J, WANG X, ZHU W, et al . MicroRNA 630 suppresses epithelial to mesenchymal transition by regulating FoxM1 in gastric cancer cells[J ] . Biochemistry (Mosc), 2017, 82(6): 707-714.DOI:10.1134/S0006297917 060074.

CHEN Y, LI Y, XUEJ, et al .Wnt-induced deubiquitination FoxM1 ensures nucleus b-catenin transactivation[J ] . EMBO J, 2016, 35(6): 668-684. DOI:10.15252/embj.2015 92810.

ZHANG W, DUAN N, ZHANG Q, et al .DNA methylation mediated down-regulation of miR-370 regulates cell growth through activation of the Wnt/β-catenin signaling pathway in human osteosarcoma cells[J ] . Int J Biol Sci, 2017, 13(5): 561-573.DOI:10.7150/ijbs.19032.

JIANG R, NIU X, HUANG Y, et al .β-Catenin is important for cancer stem cell generation and tumorogenic activity in nasopharyngeal carcinoma[J ] . Acta Biochim Biophys Sin(Shanghai), 201 6, 48(3):229-237.DOI:10.1093/abbs/gmv134.

WANG W, WEN Q, LUO J, et al .Suppression of β-catenin nuclear translocation By CGP57380 decelerates poor progression and potentiates radiation-induced apoptosis in nasopharyngeal carcinoma[J ] . Theranostics, 2017, 7(7):2134-2149.DOI:10.7150/thno.17665.

CANAVESE M, SANTO L, RAJE N.Cyclin dependent kinasesincancer: potential for therapeutic intervention[J]. Cancer Biol Ther, 2012, 13(7):451-457. DOI: 10.4161/cbt.19589.

HERMEKING H, RAGO C, SCHUHMACHER M, et al . Identification of cdk4 as a target of c-myc[J ] . Proc Natl Acad Sci USA, 2000, 97(5):2229-2234.DOI:10.1073/pnas.050586197.

ORIAN A, VAN STEENSEL B, DELROW J, et al . Genomic binding by the drosophila Myc, Max, Mad/Mnt transcription factor network[J ] . Genes Dev, 2003, 17(9):1101-1114. DOI:10.1101/gad.1066903.

WU B, CRAMPTON S P, HUGHES C C. Wnt signaling induces matrix metalloproteinase expression and regulates T cell transmigration[J]. Immunity, 2007, 26(2):227-239.DOI:10.1016/j.immuni.2006.12.007.

XUE J, LIN X, CHIU W T, et al . Sustained activation of SMAD3/SMAD4 by FoxM1 promotes TGF-β-dependent cancer metastasis[J ] . J Clin Invest, 2014, 124(2):564-579. DOI: 10.1172/JCI71104.

JOSHI K, BANASAVADI-SIDDEGOWDA Y, MO X, et al .MELK-dependent FOXM1 phosphorylation is essential for proliferation of glioma stem cells[J ] . Stem Cells, 2013, 31(6):1051-1063.DOI: 10.1002/stem.1358.

JIN B, WANG C, LI J, et al . Anthelmintic niclosamide disrupts the interplay of p65 and FOXM1/beta-catenin and eradicates leukemia stem cells in chronic myelogenous leukemia[J ] . Clin Cancer Res, 2017, 23(3):789-803.DOI:10.1158/1078-0432.CCR-16-0226.

WANG Z, AHMAD A, LI Y, et al . Forkhead box M1transcription factor: a novel target for cancer therapy[J ] . Cancer Treat Rev, 2010, 36(2):151-156.DOI:10.1016/j.ctrv.2009.11.006.

张世苹, 张旭.Wnt信号通路在肿瘤调控方面的研究进展[J].中国药理学通报, 2017, 33(1):14-18.DOI:10.3969/j.issn.1001-1978.2017.01.003.

ZHANG S P, ZHANG X. Research progress on role of Wnt signaling pathway in regulation of tumors[J]. Chin Pharmacol Bull, 2017, 33(1):14-18. DOI:10.3969/j.issn.1001-1978.2017.01.003.

0

Views

0

下载量

0

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Related Articles

Silencing calcium-activated nucleotidase 1 inhibits proliferation and migration of clear cell renal cell carcinoma 769-P cells

Vascular endothelial growth factor regulates proliferation and migration in endothelial progenitor cells through connexin 43

Histatin1 improves proliferation and migration in human human skin fibroblasts

Biological characteristics of anoikis-resistant cells from human osteosarcoma cell line hFOB1.19

Armored IL15 or IL15 receptor adaptors enhance proliferation and anti-tumor activity of CD19-targeted CAR-NK cells

Related Author

Xin LIU

Xiaobing LIU

Qian LIU

Qingqing WANG

Zhenxing YANG

Longkun LI

李禄丰

刘焕云

Related Institution

Department of Urology, Second Affiliated Hospital, Army Medical University (Third Military Medical University)

College of Life Sciences， Beijing University of Chinese Medicine

Department of Clinic Nutrition, Banan District People's Hospital of Chongqing

Department of Nutrition and Food Safety, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University)

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, College of Military Preventive Medicine, Army Medical University (Third Military Medical University)

⁰