hTERT promotes FOXM1 acetylation and subsequent invasion of gastric cancer cells

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hTERT promotes FOXM1 acetylation and subsequent invasion of gastric cancer cells

Basic Medicine | 更新时间：2026-01-09

- hTERT promotes FOXM1 acetylation and subsequent invasion of gastric cancer cells
- Journal of Third Military Medical University Vol. 39, Issue 23, Pages: 2243-2249(2017)
- 作者机构：
  
  400037 重庆，第三军医大学新桥医院消化内科
- 作者简介：
- 基金信息：
  
  the Basic Science and Frontier Technology Research Project of Chongqing(CSTC2016jcyjA0570)
- DOI：10.16016/j.1000-5404.201708132
  CLC： R345;R394.3;R735.2
- Received：22 August 2017，
  
  Revised：2017-09-18，
  
  Published：15 December 2017
- 稿件说明：
移动端阅览
Guobin LIAO, Ruikun PENG, Mengmeng JIE, et al. hTERT promotes FOXM1 acetylation and subsequent invasion of gastric cancer cells[J]. Journal of Third Military Medical University, 2017, 39(23): 2243-2249.
DOI：

Guobin LIAO, Ruikun PENG, Mengmeng JIE, et al. hTERT promotes FOXM1 acetylation and subsequent invasion of gastric cancer cells[J]. Journal of Third Military Medical University, 2017, 39(23): 2243-2249. DOI： 10.16016/j.1000-5404.201708132.

摘要

目的

2

探讨人端粒酶逆转录酶(human telomerase reverse enzyme，hTERT)促进胃癌细胞侵袭的分子机制。

方法

2

构建稳定过表达hTERT的细胞株SGC-7901-hTERT，采用Western blot检测叉头盒蛋白(forkhead box M1，FOXM1)的表达，qRT-PCR和Western blot检测FOXM1下游侵袭相关基因基质金属蛋白酶-2(matrix metalloproteinase-2，MMP-2)、基质金属蛋白酶-9(MMP-9)的mRNA和蛋白表达；构建FOXM1的shRNA干扰质粒，在SGC-7901-hTERT细胞中转染该质粒，Transwell法检测细胞侵袭能力，qRT-PCR和Western blot检测MMP-2、MMP-9的mRNA和蛋白表达；构建FOXM1启动子活性报告质粒，在SGC-7901-hTERT细胞中用双荧光素酶报告实验检测FOXM1启动子活性，qRT-PCR检测FOXM1 mRNA表达；构建稳定过表达FOXM1的细胞株SGC-7901-HA-FOXM1，并在此细胞中转染hTERT过表达质粒，免疫共沉淀(co-immunoprecipitation，Co-IP)检测FOXM1乙酰化水平变化，免疫荧光实验检测hTERT与FOXM1的细胞定位。

结果

2

与对照组比较，过表达hTERT促进FOXM1及其下游分子MMP-2、MMP-9的蛋白表达，同时也促进肿瘤细胞侵袭(

P

<

0.01)，但不影响FOXM1的启动子活性及mRNA表达；与过表达hTERT组比较，干扰FOXM1可抑制MMP-2、MMP-9的mRNA和蛋白表达，同时也抑制肿瘤细胞侵袭(

P

<

01)；hTERT与FOXM1存在细胞共定位，且过表达hTERT可上调FOXM1乙酰化水平。

结论

2

hTERT通过上调FOXM1乙酰化促进胃癌细胞侵袭。

Abstract

Objective

2

To investigate the molecular mechanism of human telomerase reverse transcriptase (hTERT) in promoting the invasion of gastric cancer cells.

Methods

2

A cell line with stable expression of hTERT

SGC-7901-hTERT was constructed based on human gastric cancer SGC-7901 cells. Western blotting was used to detect the expression of forkhead box M1 (FOXM1)

and it combined with qRT-PCR to measure the expression of FOXM1 downstream molecules

matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at protein and mRNA levels. The shRNA interference plasmid of FOXM1 was constructed and transfected into the SGC-7901-hTERT cells. Transwell chamber test was used to detect the invasive ability of the cells. qRT-PCR and Western blotting were used again for the expression of MMP-2 and MMP-9. The activity of FOXM1 promoter was detected by double luciferase reporter assay in SGC-7901-hTERT cells and corresponding control cells

and then the mRNA expression of FOXM1 was detected by qRT-PCR. After the construction of SGC-7901 FOXM1-HA cells with FOXM1-HA lentivirus

the cells were transfected with hTERT overexpression plasmid. The acetylation of FOXM1 was detected by co-immunoprecipitation (Co-IP). The immunofluorescence assay was used to detect the co-localization of hTERT and FOXM1.

Results

2

Compared with the control group

hTERT overexpression promoted the expression of FOXM1 protein

which facilitated the expression of FOXM1 target genes

MMP-2 and MMP-9

and also promoted tumor cell invasion (

P

<

01). However

the expression of FOXM1 mRNA and its promoter activity was not affected. Compared with the overexpressing hTERT group

interference of FOXM1 partially decreased the effect of hTERT-promoted FOXM1 target gene expression and reduced the hTERT-mediated invasion of SGC-7901 cells (

P

<

01). FOXM1 and hTERT were co-localized in the SGC-7901 cells

and overexpression of hTERT up-regulated the level of acetylation of FOXM1.

Conclusions

2

hTERT affects the invasion of gastric cancer cells by up-regulation of FOXM1 acetylation.

关键词

Keywords

references

[WHO. World Health Rankings:Stomach cancer [EB/OL ] . [2017-08-22 ] . http://www.worldlifeexpectancy.com/cause-of-death/stomach-cancer/by-country/ http://www.worldlifeexpectancy.com/cause-of-death/stomach-cancer/by-country/ .

ZHENG R, ZENG H, ZHANG S, et al . National estimates of cancer prevalence in China, 2011[J ] . Cancer Lett, 2016, 370(1): 33-38. DOI:10.1016/j.canlet.2015.10.003.

ZHU L, QIN J, WANG J, et al . Early gastric cancer: current advances of endoscopic diagnosis and treatment[J ] . Gastroenterol Res Pract, 2016, 2016: 9638041. DOI:10.1155/2016/9638041.

XU Y, HUA J, LI J, et al . Laparoscopic versus open gastrectomy for gastric cancer with serous invasion: long-term outcomes[J ] . J Surg Res, 2017, 215: 190-195. DOI:10.1016/j.jss.2017.03.048.

QIN Y, GUO H, TANG B, et al . The non-reverse transcriptase activity of the human telomerase reverse transcriptase promotes tumor progression (review)[J ] . Int J Oncol, 2014, 45(2): 525-531. DOI:10.3892/ijo.2014.2470.

ZHOU J, DING D, WANG M, et al . Telomerase reverse transcriptase in the regulation of gene expression[J ] . BMB Rep, 2014, 47(1): 8-14. DOI:10.5483/bmbrep.2014.47.1.284.

KHATTAR E, KUMAR P, LIU C Y, et al . Telomerase reverse transcriptase promotes cancer cell proliferation by augmenting tRNA expression[J ] . J Clin Invest, 2016, 126(10): 4045-4060. DOI:10.1172/JCI86042.

LIN G, CHEN T, ZOU J, et al . Quantum dots-siRNA nanoplexes for gene silencing in central nervous system tumor cells[J ] . Front Pharmacol, 2017, 8: 182. DOI:10.3389/fphar.2017.00182.

CHAKRABARTI M, BANIK N L, RAY S K. Sequential hTERT knockdown and apigenin treatment inhibited invasion and proliferation and induced apoptosis in human malignant neuroblastoma SK-N-DZ and SK-N-BE2 cells[J]. J Mol Neurosci, 2013, 51(1): 187-198. DOI:10.1007/s12031-013-9975-x.

CHEN P C, PENG J R, HUANG L, et al . Overexpression of human telomerase reverse transcriptase promotes the motility and invasiveness of HepG2 cells in vitro [J ] . Oncol Rep, 2013, 30(3): 1157-1164. DOI:10.3892/or.2013.2563..

HU C, NI Z, LI B S, et al . hTERT promotes the invasion of gastric cancer cells by enhancingFOXO3a ubiquitination and subsequent ITGB1 upregulation[J ] . Gut, 2017, 66(1): 31-42. DOI:10.1136/gutjnl-2015-309322.

WIERSTRA I. FOXM1 (Forkhead box M1) in tumorigenesis: overexpression in human cancer, implication in tumorigenesis, oncogenic functions, tumor-suppressive properties, and target of anticancer therapy[J]. Adv Cancer Res, 2013, 119: 191-419. DOI:10.1016/B978-0-12-407190-2.00016-2.

HU C, LIU D, ZHANG Y, et al . LXRα-mediated downregulation of FOXM1 suppresses the proliferation of hepatocellular carcinoma cells[J ] . Oncogene, 2014, 33(22): 2888-2897. DOI:10.1038/onc.2013.250.

YU M, TANG Z, MENG F, et al . Elevated expression of FoxM1 promotes the tumor cell proliferation in hepatocellular carcinoma[J ] . Tumour Biol, 2016, 37(1): 1289-1297. DOI:10.1007/s13277-015-3436-9.

NAKAMURA S, HIRANO I, OKINAKA K, et al . The FOXM1 transcriptional factor promotes the proliferation of leukemia cells through modulation of cell cycle progression in acute myeloid leukemia[J ] . Carcinogenesis, 2010, 31(11): 2012-2021. DOI:10.1093/carcin/bgq185.

DAI B, KANG S H, GONG W, et al . Aberrant FoxM1B expression increases matrix metalloproteinase-2 transcription and enhances the invasion of glioma cells[J ] . Oncogene, 2007, 26(42): 6212-6219. DOI:10.1038/sj.onc.1210443.

JIN H, LI X J, PARK M H, et al . FOXM1-mediated downregulation of uPA and MMP9 by 3, 3′-diindolylmethane inhibits migration and invasion of human colorectal cancer cells[J ] . Oncol Rep, 2015, 33(6): 3171-3177. DOI:10.3892/or.2015.3938.

DING D, XI P, ZHOU J, et al . Human telomerase reverse transcriptase regulates MMP expression independently of telomerase activity via NF-κB-dependent transcription[J ] . FASEB J, 2013, 27(11): 4375-4383. DOI:10.1096/fj.13-230904..

YU S T, CHEN L, WANG H J, et al . hTERT promotes the invasion of telomerase-negative tumor cells in vitro [J ] . Int J Oncol, 2009, 35(2): 329-336..

YANG L, CUI M, ZHANG L, et al . FOXM1 facilitates gastric cancer cell migration and invasion by inducing cathepsin D.[J ] . Oncotarget, 2017. DOI: 10.18632/oncotarget.19254.

MAJOR M L, LEPE R, COSTA R H. Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivators[J]. Mol Cell Biol, 2004, 24(7): 2649-2661. DOI:10.1128/mcb.24.7.2649-2661.2004.

COHN O, FELDMAN M, WEIL L, et al . Chromatin associated SETD3 negatively regulates VEGF expression[J ] . Sci Rep, 2016, 6: 37115. DOI:1 0.1038/srep37115.

LV C, ZHAO G, SUN X, et al . Acetylation of FOXM1 is essential for its transactivation and tumor growth stimulation[J ] . Oncotarget, 2016, 7(37): 60366-60382. DOI:10.18632/oncotarget.11332.

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