|Table of Contents|

Effects of METTL14-mediated m6A methylation modifying Snail-1 protein on invasion and epithelial mesenchymal transformation of esophageal carcinoma cells

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

Issue:
2023 19
Page:
3565-3571
Research Field:
Publishing date:

Info

Title:
Effects of METTL14-mediated m6A methylation modifying Snail-1 protein on invasion and epithelial mesenchymal transformation of esophageal carcinoma cells
Author(s):
ZHONG Shouping; LI Guangshun
Cardiothoracic Surgery,Xi'an Central Hospital,Shaanxi Xi'an 710004,China.
Keywords:
METTL14; m6A; Snail-1; esophageal carcinoma; EMT
PACS:
R735.1
DOI:
10.3969/j.issn.1672-4992.2023.19.006
Abstract:
Objective:To investigate the effect and mechanism of METTL14-mediated m6A methylation modifying Snail-1 protein in esophageal squamous cell carcinoma(ESCC) invasion and epithelial mesenchymal transformation(EMT).Methods:GEPIA was used to analyze the expression of METTL14 in ESCC patients and to evaluate their survival.The experiment was divided into si-NC group and si-METTL14 group.The expression of METTL14 gene was detected by qPCR.The expressions of Snail-1 and EMT-related proteins(E-cadherin,N-cadherin and Vimentin) were detected by Western blot.Transwell test was used to detect cell invasion ability.The level of m6A modified Snail-1 was detected by MeRIP-qPCR.The stability of Snail-1 mRNA was detected by adding actinomycin D.Results:The expression of METTL14 was significantly increased in ESCC patients and cell lines(P<0.01).Overall survival was significantly shortened in patients with high expression of METTL14(P<0.01).The mRNA and protein expression levels of METTL14 were significantly decreased in si-METTL14 group(P<0.01).E-cadherin expression was significantly increased(P<0.01),while the expressions of N-cadherin and Vimentin were significantly decreased(P<0.01).The number of cell migration was significantly decreased(P<0.01).Further,si-METTL14 transfection significantly down-regulated Snail-1 mRNA and protein levels(P<0.01),and significantly reduced m6A Snail-1 levels(P<0.01) and Snail-1 mRNA stability(P<0.01).Snail-1 rescue experiment showed that the expression of E-cadherin in si-METTL14+OE-Snail-1 group significantly decreased compared with that in si-METTL14+OE-NC group(P<0.01),the expressions of N-cadherin and Vimentin were significantly increased(P<0.01).Conclusion:The expressions of METTL14 and Snail-1 were up-regulated in ESCC cells.METTL14 knockdown significantly reduced the stability of Snail-1 mRNA and reduced its expression,thus inhibiting ESCC cell invasion and EMT process.

References:

[1] SUNG H,FERLAY J,SIEGEL RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin,2021,71(3):209-249.
[2] 曹雅杰,包晓红,李书珍,等.胰岛素样生长因子1受体抑制剂NVP-AEW541对ESCC细胞增殖、迁移和侵袭的影响及其机制［J］.吉林大学学报(医学版),2021,47(05):1131-1138. CAO YJ,BAO XH,LI SZ,et al.Effects of insulin-like growth factor 1 receptor inhibitor NVP-AEW541 on proliferation,migration and invasion of ESCC cells and its mechanism［J］.Journal of Jilin University(Medical Edition),2021,47(05):1131-1138.
[3] 陈文浩,杨明,张艳桥.上皮-间质转化在恶性肿瘤中发生机制的研究进展［J］.中国肿瘤,2016,25(01):51-57. CHEN WJ,YANG M,ZHANG YQ.Study on the mechanism of epithelial-mesenchymal transformation in malignant tumors ［J］.Chinese Tumor,2016,25(01):51-57.
[4] 金凤,刘延庆,钱亚云.哺乳动物雷帕霉素靶蛋白与恶性肿瘤上皮间质转化研究进展［J］.医学综述,2016,22(05):896-899. JIN F,LIU YQ,QIAN YY .Advances in mammalian target proteins of rapamycin and epithelial mesenchymal transformation in malignant tumors［J］.Medical Review,2016,22(05):896-899.
[5] 郝小军,畅智慧,赵相轩.miRNA调控EMT影响结直肠癌侵袭转移的研究进展［J］.现代肿瘤医学,2017,25(01):142-145. HE XJ,CHANG ZH,ZHAO XX.Research progress on the effect of miRNA regulation on the invasion and metastasis of colorectal cancer［J］.Modern Oncology,2017,25(01):142-145.
[6] RONG D,WU F,LU C,et al.m6A modification of circHPS5 and hepatocellular carcinoma progression through HMGA2 expression［J］.Mol Ther Nucleic Acids,2021,26:637-648.
[7] ZHANG C,HUANG S,ZHUANG H,et al.YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation［J］.Oncogene,2020,39(23):4507-4518.
[8] WU Y,YANG X,CHEN Z,et al.m(6)A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1［J］.Mol Cancer,2019,18(1):87.
[9] ZHANG N,HUA X,TU H,et al.Isorhapontigenin(ISO) inhibits EMT through FOXO3A/METTL14/VIMENTIN pathway in bladder cancer cells［J］.Cancer Lett,2021,520:400-408.
[10] LIU X,XIAO M,ZHANG L,et al.The m6A methyltransferase METTL14 inhibits the proliferation,migration,and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway［J］.J Clin Lab Anal,2021,35(3):e23655.
[11] CHEN X,XU M,XU X,et al.METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer［J］.Mol Cancer,2020,19(1):106.
[12] HEMMATZADEH M,MOHAMMADI H,BABAIE F,et al.Snail-1 silencing by siRNA inhibits migration of TE-8 esophageal cancer cells through downregulation of metastasis-related genes［J］.Adv Pharm Bull,2018,8(3):437-445.
[13] WANG Y,SHI J,CHAI K,et al.The role of snail in EMT and tumorigenesis［J］.Curr Cancer Drug Targets,2013,13(9):963-972.
[14] LI S,LU J,CHEN Y,et al.MCP-1-induced ERK/GSK-3beta/Snail signaling facilitates the epithelial-mesenchymal transition and promotes the migration of MCF-7 human breast carcinoma cells［J］.Cell Mol Immunol,2017,14(7):621-630.
[15] LIN X,CHAI G,WU Y,et al.RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail［J］.Nat Commun,2019,10(1):2065.
[16] QIAO K,CHEN C,LIU H,et al.Pinin induces epithelial-to-mesenchymal transition in hepatocellular carcinoma by regulating m6A modification［J］.J Oncol,2021,2021:7529164.
[17] 王晓坤,杨欢,范金虎,等.代谢组学在食管癌早期诊断与应用中的研究进展［J］.中国肿瘤,2022,31(10):803-808. WANG XK,YANG H,FAN JH,et al.Research progress of metabonomics in early diagnosis and application of esophageal cancer［J］.Chinese Tumor,2022,31(10):803-808.
[18] ZHENG G,DAHL JA,NIU Y,et al.ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility［J］.Mol Cell,2013,49(1):18-29.
[19] GALLAGHER EJ,LEROITH D.Obesity and diabetes:The increased risk of cancer and cancer-related mortality［J］.Physiol Rev,2015,95(3):727-748.
[20] CHEN X,YU C,GUO M,et al.Down-regulation of m6A mRNA methylation is involved in dopaminergic neuronal death［J］.ACS Chem Neurosci,2019,10(5):2355-2363.
[21] WANG S,SUN C,LI J,et al.Roles of RNA methylation by means of N(6)-methyladenosine m(6)A in human cancers［J］.Cancer Lett,2017,408:112-120.
[22]陈俊文,王侠,王科峰.RNA m6A修饰与肿瘤［J］.现代肿瘤医学，2020，28（18）： 3248-3254. CHEN JW,WANG X,WANG KF.N6-methyladenosine RNA modification and cancers［J］.Modern Oncology，2020，28（18）： 3248-3254.
[23] CHEN XY,ZHANG J,ZHU JS.The role of m(6)A RNA methylation in human cancer［J］.Mol Cancer,2019,18(1):103.
[24] WENG H,HUANG H,WU H,et al.METTL14 inhibits hematopoietic stem/progenitor differentiation and promotes leukemogenesis via mRNA m(6)A modification［J］.Cell Stem Cell,2018,22(2):191-205.
[25] WANG M,LIU J,ZHAO Y,et al.Upregulation of METTL14 mediates the elevation of PERP mRNA N(6) adenosine methylation promoting the growth and metastasis of pancreatic cancer［J］.Mol Cancer,2020,19(1):130.
[26] SUN T,WU Z,WANG X,et al.LNC942 promoting METTL14-mediated m(6)A methylation in breast cancer cell proliferation and progression［J］.Oncogene,2020,39(31):5358-5372.
[27] PANNEERDOSS S,EEDUNURI VK,YADAV P,et al.Cross-talk among writers,readers,and erasers of m(6)A regulates cancer growth and progression［J］.Sci Adv,2018,4(10):8263.
[28] LIU Z,WU K,GU S,et al.A methyltransferase-like 14/miR-99a-5p/tribble 2 positive feedback circuit promotes cancer stem cell persistence and radioresistance via histone deacetylase 2-mediated epigenetic modulation in esophageal squamous cell carcinoma［J］.Clin Transl Med,2021,11(9):545.
[29] WIECZOREK-SZUKALA K and LEWINSKI A.The role of Snail-1 in thyroid cancer-what we know so far［J］.J Clin Med,2021,10(11):2324.
[30] FAN F,SAMUEL S,EVANS KW,et al.Overexpression of snail induces epithelial-mesenchymal transition and a cancer stem cell-like phenotype in human colorectal cancer cells［J］.Cancer Med,2012,1(1):5-16.
[31] MEZENCEV R,MATYUNINA LV,JABBARI N,et al.Snail-induced epithelial-to-mesenchymal transition of MCF-7 breast cancer cells:systems analysis of molecular changes and their effect on radiation and drug sensitivity［J］.BMC Cancer,2016,16:236.
[32] OSORIO LA,FARFAN NM,CASTELLON EA,et al.SNAIL transcription factor increases the motility and invasive capacity of prostate cancer cells［J］.Mol Med Rep,2016,13(1):778-786.
[33] 马平川,何宏月,王芳,等.上皮间质转化相关蛋白E-cadherin、N-cadherin及Snail在子宫内膜异位症相关卵巢癌的表达及意义［J］.实用妇产科杂志,2016,32(03):211-215. MA PC,HE HY,WANG F,et al.Expression and significance of epithelial interstitial transition related proteins E-cadherin,N-cadherin and Snail in endometriosis related ovarian cancer［J］.Journal of Practical Obstetrics and Gynecology,2016,32(03):211-215.
[34] 瞿昌晶,王铮元,崔嵘嵘,等.miR-34在胃癌组织中的表达及与EMT、化疗耐药性的相关性［J］.现代肿瘤医学,2022,30(16):2952-2956. QU JJ,WANG ZY,CUI RR,et al.Expression of miR-34 in gastric cancer tissues and its correlation with EMT and chemotherapy resistance［J］.Modern Oncology,2022,30(16):2952-2956.

Memo

Memo:
-
Last Update: 2023-08-31