浏览全部资源
扫码关注微信
TET1基因对肺癌细胞迁移和侵袭能力的影响
Effect of TET1 gene expression on migration and invasion in lung cancer cells
- 第三军医大学学报 2020年42卷第13期 页码：1279-1285
- 作者机构：
1.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系毒理学研究所
2.650224 昆明，云南省昆明云桥医院急诊医学科
- 作者简介：
[ 刘文斌，E-mail：wenbinliutmmu@sina.com LIU Wenbin, E-mail:wenbinliutmmu@sina.com
- 基金信息：国家自然科学基金面上项目(81573114);国家自然科学基金面上项目(81872659);重庆市自然科学基金面上项目(CSTC2018jcyjAX0233)
DOI：10.16016/j.1000-5404.202002114
中图分类号： R394.3;R730.23;R734.2收稿：2020-02-17，
修回：2020-03-06，
纸质出版：2020-07-15
- 稿件说明：
移动端阅览
李艳, 陈洪强, 刘晋祎, 等. TET1基因对肺癌细胞迁移和侵袭能力的影响[J]. 第三军医大学学报, 2020,42(13):1279-1285.
Yan LI, Hongqiang CHEN, Jinyi LIU, et al. Effect of TET1 gene expression on migration and invasion in lung cancer cells[J]. Journal of Third Military Medical University, 2020, 42(13): 1279-1285.
李艳, 陈洪强, 刘晋祎, 等. TET1基因对肺癌细胞迁移和侵袭能力的影响[J]. 第三军医大学学报, 2020,42(13):1279-1285. DOI： 10.16016/j.1000-5404.202002114.
Yan LI, Hongqiang CHEN, Jinyi LIU, et al. Effect of TET1 gene expression on migration and invasion in lung cancer cells[J]. Journal of Third Military Medical University, 2020, 42(13): 1279-1285. DOI： 10.16016/j.1000-5404.202002114.
摘要
目的
2
探讨TET1基因表达水平对肺癌细胞迁移和侵袭能力的影响及其作用机制。
方法
2
采用RT-qPCR检测正常支气管上皮细胞及肺癌细胞株中TET1基因的表达水平；通过构建TET1基因过表达和敲低表达肺癌细胞模型，采用划痕愈合实验和Transwell实验分析TET1基因不同表达水平对肺癌细胞迁移及侵袭能力的影响；通过RT-qPCR和蛋白印迹法对TET1下游调控基因β-catenin(CTNNB1)、MMP7的mRNA及蛋白表达水平进行检测并确定其可能的信号通路。
结果
2
多种肺癌细胞中TET1基因表达水平较之正常支气管上皮细胞(human bronchial epithelial，HBE)均呈现显著下降(
P
<
0.01)。过表达TET1基因可明显抑制肺癌细胞迁移和侵袭能力，而敲低TET1基因表达水平后肺癌细胞侵袭及迁移能力明显增强(
P
<
0.01)；m
RNA及蛋白表达水平检测发现，过表达TET1基因后其下游基因CTNNB1、MMP7的表达水平明显下降(
P
<
0.01)，而敲低TET1基因表达后其下游基因CTNNB1、MMP7的表达水平显著上升(
P
<
0.01)。β-catenin信号通路抑制剂处理可显著降低TET1对肺癌细胞迁移和侵袭的作用。
结论
2
TET1基因表达在多种肺癌细胞株中显著下降。TET1基因可能通过Wnt/β-catenin信号通路及其关键基因CTNNB1、MMP7的表达水平抑制肺癌细胞的迁移及侵袭。
Abstract
Objective
2
To explore the effect of ten-eleven translocation family 1 (TET1) gene expression on the migration and invasion of lung cancer cells and investigate its underlying mechanism.
Methods
2
The expression level of TET1 gene in normal human bronchial epithelial (HBE) cells and lung cancer cell lines (H460
H358
95D and LTEP-a-2) was detected by quantitative RT-PCR. The effects of different expression level (overexpression and knockdown) of TET1 gene on the migration and invasion ability in lung cancer cells was analyzed by wound healing experiment and Transwell assay. The mRNA and protein expression levels of downstream regulatory gene β-catenin (CTNNB1) and MMP7 were detected by quantitative RT-PCR and Western blotting to determine the possible signal pathway.
Results
2
The expression level of TET1 gene was decreased in lung cancer cells compared with normal HBE cells (
P
<
0.01). Overexpression of TET1 gene significantly inhibited the migration and invasion of lung cancer cells
while its knockdown enhanced the invasion and migration abilities of lung cancer cells (
P
<
0.01). The mRNA and protein expression levels of CTNNB1 and MMP7 were decreased after TET1 overexpression
while the mRNA and protein levels of the 2 molecules were increased after knockdown (
P
<
0.01). Blockade of CTNNB1 by its inhibitor significantly diminished the effect of TET1 on the migration and invasion of lung cancer cell lines.
Conclusion
2
The expression level of TET1 is down-regulated in lung cancer cell lines. TET1 gene may inhibit the migration and invasion of lung cancer cells mainly through Wnt/β-catenin signaling pathway and its key downstream genes CTNNB1 and MMP7.
关键词
Keywords
references
BIRKBAK N J, MCGRANAHAN N. Cancer genome evolutionary trajectories in metastasis[J]. Cancer Cell, 2020, 37(1): 8-19. DOI:10.1016/j.ccell.2019.12.004.
SUN Z X, XU X G, HE J L, et al . EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity[J ] . Nat Commun, 2019, 10(1): 3892. DOI:10.1038/s41467-019-11905-3.
YANG X W, WONG M P M, NG R K. Aberrant DNA methylation in acute myeloid leukemia and its clinical implications[J]. Int J Mol Sci, 2019, 20(18): E4576. DOI:10.3390/ijms20184576.
ALOIA L, MCKIE M A, VERNAZ G, et al . Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration[J ] . Nat Cell Biol, 2019, 21(11): 1321-1333. DOI:10.1038/s41556-019-0402-6.
ZHANG Y P, ZHANG Y D, CHEN D M, et al . Genome-wide alteration of 5-hydroxymethylcytosine in hypoxic-ischemic neonatal rat model of cerebral palsy[J ] . Front Mol Neurosci, 2019, 12: 214. DOI:10.3389/fnmol.2019.00214.
WU H X, CHEN Y X, WANG Z X, et al . Alteration in TET1 as potential biomarker for immune checkpoint blockade in multiple cancers[J ] . J Immunother Cancer, 2019, 7(1): 264. DOI:10.1186/s40425-019-0737-3.
WU J, LI H Z, SHI M M, et al . TET1-mediated DNA hydroxymethylation activates inhibitors of the Wnt/β-catenin signaling pathway to suppress EMT in pancreatic tumor cells[J ] . J Exp Clin Cancer Res, 2019, 38(1): 348. DOI:10.1186/s13046-019-1334-5.
SU P H, HSU Y W, HUANG R L, et al . TET1 promotes 5hmC-dependent stemness, and inhibits a 5hmC-independent epithelial-mesenchymal transition, in cervical precancerous lesions[J ] . Cancer Lett, 2019, 450: 53-62. DOI:10.1016/j.canlet.2019.01.033
KAHN M. Can we safely target the WNT pathway?[J]. Nat Rev Drug Discov, 2014, 13(7): 513-532. DOI:10.1038/nrd4233.
PATEL S, ALAM A, PANT R, et al . Wnt signaling and its significance within the tumor microenvironment: novel therapeutic insights[J ] . Front Immunol, 2019, 10: 2872. DOI:10.3389/fimmu.2019.02872.
WU B K, BRENNER C. Suppression of TET1-dependent DNA demethylation is essential for KRAS-mediated transformation[J]. Cell Rep, 2014, 9(5): 1827-1840. DOI:10.1016/j.celrep.2014.10.063.
FILIPCZAK P T, LENG S G, TELLEZ C S, et al . P53-suppressed oncogene TET1 prevents cellular aging in lung cancer[J ] . Cancer Res, 2019, 79(8): 1758-1768. DOI:10.1158/0008-5472.CAN-18-1234.
YOKOYAMA S, HIGASHI M, TSUTSUMIDA H, et al . TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer[J ] . Genes Cancer, 2017, 8(3/4): 517-527. DOI:10.18632/genesandcancer.139.
COLLIGNON E, CANALE A, AL WARDI C, et al . Immunity drives TET1 regulation in cancer through NF-κB[J ] . Sci Adv, 2018, 4(6): eaap7309. DOI:10.1126/sciadv.aap7309.
PUTIRI E L, TIEDEMANN R L, THOMPSON J J, et al . Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells[J ] . Genome Biol, 2014, 15(6): R81. DOI:10.1186/gb-2014-15-6-r81
GUO H L, ZHU H Y, ZHANG J, et al . TET1 suppresses colon cancer proliferation by impairing β-catenin signal pathway[J ] . J Cell Biochem, 2019, 120(8): 12559-12565. DOI:10.1002/jcb.28522.
0
浏览量
0
下载量
0
CSCD
- 网络PDF下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
