提高m6A去甲基化酶FTO表达抑制鼻咽癌细胞增殖

doi:10.16352/j.issn.1001-6325.2024.01.0057

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (1): 57-62.doi: 10.16352/j.issn.1001-6325.2024.01.0057

提高m⁶A去甲基化酶FTO表达抑制鼻咽癌细胞增殖

廖镇城^1,2, 杨思懿¹, 吴平安^1*

1.香港大学深圳医院耳鼻咽喉头颈外科,广东深圳 518000;
2.深圳大学医学部,广东深圳 518000

收稿日期:2022-11-01 修回日期:2023-10-24 出版日期:2024-01-05 发布日期:2023-12-25
通讯作者: ^*:wupa@hku-szh.org
基金资助:
深圳市科技研发资金基础研究专项(JCYJ20220530142413031);香港大学深圳医院临床肿瘤科深圳市癌症转移与个体化治疗重点实验室 (ZDSYS20210623091811035)

Increased expression of m⁶A demethylase FTO inhibits the proliferation of nasopharyngeal carcinoma cells

LIAO Zhencheng^1,2, YANG Siyi¹, WU Ping'an^1*

1. Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, the University of Hong Kong-Shenzhen Hospital, Shenzhen 518000;
2. Department of Medicine, Shenzhen University, Shenzhen 518000, China

Received:2022-11-01 Revised:2023-10-24 Online:2024-01-05 Published:2023-12-25
Contact: ^*:wupa@hku-szh.org

摘要/Abstract

摘要： 目的探究N6-甲基腺嘌呤(m⁶A)去甲基化酶人类脂肪和肥胖相关(FTO)蛋白在鼻咽癌(NPC)中的表达水平,以及过表达FTO对鼻咽癌体内外增殖的影响。方法用免疫组织化学检测鼻咽癌组织及癌旁组织中FTO蛋白的表达;筛选FTO的优势表达细胞株,构建过表达FTO细胞株,用软琼脂增殖实验验证;建立小鼠成瘤模型,测量肿瘤的生长速度。结果发现FTO在鼻咽癌组织中较癌旁组织低表达。FTO低表达促进了鼻咽癌细胞的增殖,而过表达FTO则可逆转这种作用。结论 FTO抑制鼻咽癌细胞的增殖过程,可为寻找鼻咽癌的治疗靶点提供实验依据,FTO 可能成为未来 NPC 的治疗靶点。

关键词: 鼻咽癌, N6-甲基腺嘌呤, 人类脂肪和肥胖相关蛋白, 细胞增殖

Abstract: Objective To investigate the expression of N6 methyladenine (m6A) demethylase human fat mass and obesity-associated(FTO) protein in nasopharyngeal carcinoma (NPC), and the effect of over-expression of FTO on the proliferation of nasopharyngeal carcinoma in vitro and in vivo. Methods Immunohistochemistry method was used to detect the expression of FTO protein in nasopharyngeal carcinoma tissues and para-cancerous tissues; The dominant expression cell line of FTO was screened, the over-expression FTO cell line was constructed. The cell proliferation was examined by soft-agar method. A mouse tumor model was developed for measurement of tumor growth. Results The expression of FTO in nasopharyngeal carcinoma tissues was lower than that in adjacent tissues. Low expression of FTO promoted proliferation of NPC cells, while over-expression of FTO reversed this effect. Conclusions FTO inhibits proliferation of nasopharyngeal carcinoma and this result may provide an experimental technology in searching therapeutic targets of chemotherapy for nasopharyngeal carcinoma.

Key words: nasopharyngeal carcinoma, N6-methyladenosine, human fat mass and obesity-associated proteins, cell proliferation

中图分类号:

R739.63

廖镇城, 杨思懿, 吴平安. 提高m⁶A去甲基化酶FTO表达抑制鼻咽癌细胞增殖[J]. 基础医学与临床, 2024, 44(1): 57-62.

LIAO Zhencheng, YANG Siyi, WU Ping'an. Increased expression of m⁶A demethylase FTO inhibits the proliferation of nasopharyngeal carcinoma cells[J]. Basic & Clinical Medicine, 2024, 44(1): 57-62.

参考文献 15

[1]	Limkin EJ, Blanchard P. Does East meet West? Towards a unified vision of the management of nasopharyngeal carcinoma[J]. Br J Radiol, 2019, 92: 20190068. doi:10.1259/bjr.20190068.
[2]	Sun T, Wu R, Ming L. The role of m6A RNA methylation in cancer[J]. Biomed Pharmacother, 2019, 112: 108613.doi: 10.1016/j.biopha.2019.108613.
[3]	Wang T, Kong S, Tao M, et al. The potential role of RNA N6-methyladenosine in cancer progression[J]. Mol Cancer, 2020, 19: 88.doi: 10.1186/s12943-020-01204-7.
[4]	Jia G, Fu Y, Zhao X, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO[J]. Nat Chem Biol, 2011, 7: 885-887.
[5]	Xiao Y, Thakkar KN, Zhao H, et al. The mA RNA demethylase FTO is a HIF-independent synthetic lethal partner with the VHL tumor suppressor [J]. Proc Natl Acad Sci U S A, 2020, 117: 21441-21449.
[6]	Niu Y, Lin Z, Wan A, et al. RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3[J]. Mol Cancer, 2019, 18: 46.doi: 10.1186/s12943-019-1004-4.
[7]	Taketo K, Konno M, Asal A, et al. The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells[J]. Int J Oncol, 2018, 52: 621-629.
[8]	Su R, Dong L, Li C, et al. R-2HG exhibits anti-tumor activity by targeting FTO/mA/MYC/CEBPA signaling[J]. Cell, 2018, 172.doi: 10.1016/j.cell.2017.11.031
[9]	Song L, Liu Z, Hu HH, et al. Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy[J]. Nat Commun, 2020, 11: 5842.doi: 10.1038/s41467-020-19694-w.
[10]	Li W, Lu H, Wang H, et al. Circular RNA TGFBR2 acts as a ceRNA to suppress nasopharyngeal carcinoma progression by sponging miR-107[J]. Cancer Lett, 2021, 499: 301-313.
[11]	Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma[J]. Cancer Epidemiol Biomarkers Prev, 2006, 15: 1765-1777.
[12]	Li J, Zhu L, Shi Y, et al. m6A demethylase FTO promotes hepatocellular carcinoma tumorigenesis via mediating PKM2 demethylation[J]. Am J Transl Res, 2019, 11: 6084-6092.
[13]	Cui Y, Zhang C, Ma S, et al. RNA m6A demethylase FTO-mediated epigenetic up-regulation of LINC00022 promotes tumorigenesis in esophageal squamous cell carcino-ma[J]. J Exp Clin Cancer Res, 2021, 40: 294.doi: 10.1186/s13046-021-02096-1.
[14]	Tao L, Mu X, Chen H, et al. FTO modifies the m6A level of MALAT and promotes bladder cancer progression[J]. Clin Transl Med, 2021, 11: e310.doi: 10.1002/ctm2.310.
[15]	Huang J, Sum W, Wang Z, et al. FTO suppresses glycolysis and growth of papillary thyroid cancer via decreasing stability of APOE mRNA in an N6-methyladenosine-dependent manner[J]. J Exp Clin Cancer Res, 2022, 41: 42.doi: 10.1186/s13046-022-02254-z.

提高m⁶A去甲基化酶FTO表达抑制鼻咽癌细胞增殖

Increased expression of m⁶A demethylase FTO inhibits the proliferation of nasopharyngeal carcinoma cells

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 15

相关文章 15

编辑推荐

Metrics

本文评价

[1]	潘闪, 林铿强, 陈树兴. 培美曲塞抑制人肺腺癌细胞系A549增殖[J]. 基础医学与临床, 2023, 43(9): 1359-1363.
[2]	梁辉勇, 韦秋慧, 丁亚, 彭小青, 姚静, 苏齐鉴. 虫草素抑制TNF-α诱导的人角质形成细胞系HaCaT增殖[J]. 基础医学与临床, 2023, 43(9): 1390-1393.
[3]	张培波, 李义. 沙棘总黄酮抑制膀胱癌细胞系T24增殖[J]. 基础医学与临床, 2023, 43(7): 1122-1126.
[4]	侯孟杰, 赵娜, 黄富强, 王亚南, 刘芳铭. 载脂蛋白E通过降低高尔基体膜蛋白73表达抑制小鼠肝癌细胞系增殖[J]. 基础医学与临床, 2023, 43(5): 762-770.
[5]	王芳芳, 曹慧媛, 汪婧, 王宁, 黄国良. 上调miR-200c-5p的表达抑制人结直肠癌细胞系SW480增殖[J]. 基础医学与临床, 2023, 43(2): 241-245.
[6]	刘爱霞, 张浩, 孙杰, 杨丽华, 赵晓涛. GPS2对肝癌细胞系MHCC-97H增殖、迁移与侵袭的调控作用[J]. 基础医学与临床, 2023, 43(12): 1784-1791.
[7]	张珍珍, 李洋, 高生宝, 夏德鑫, 严玉兰. 重组新城疫病毒rL-RVG抑制人肺腺癌细胞系增殖[J]. 基础医学与临床, 2023, 43(10): 1549-1556.
[8]	沈永华, 汪峻峰, 程泽星, 冯娟娟. 秦皮甲素抑制人鼻咽癌细胞系HNE-3增殖[J]. 基础医学与临床, 2022, 42(8): 1237-1242.
[9]	江宁, 郭钧, 刘铖, 周举. 莪术醇抑制人骨肉瘤细胞系的增殖和促凋亡[J]. 基础医学与临床, 2022, 42(8): 1200-1205.
[10]	赵霞, 蔡庆春, 丁瑞敏, 张倩. 华蟾素抑制人鼻咽癌细胞系CNE2和HONE1增殖[J]. 基础医学与临床, 2022, 42(3): 436-440.
[11]	陈建苗. DFG-STYK1/NOK对小鼠胚胎成纤维细胞系NIH3T3增殖以及细胞周期G₁/S的影响[J]. 基础医学与临床, 2021, 41(6): 859-864.
[12]	刘亚琪, 郑承红. miR-205通过靶向调控Wnt-5a抑制乳头状甲状腺癌的细胞增殖[J]. 基础医学与临床, 2021, 41(3): 358-363.
[13]	张文婷, 王瑾, 岳继萍, 靳文文, 张志楠, 焦向英. 硫氧还蛋白相互作用蛋白降低GLP-1促小鼠胰岛β细胞的增殖效应[J]. 基础医学与临床, 2020, 40(8): 1076-1082.
[14]	雷巧丽, 饶奇斌, 林泽文. 牛磺酸联合SN50协同抑制人肝癌细胞系HepG2的增殖[J]. 基础医学与临床, 2020, 40(3): 340-345.
[15]	苗加伟, 陈洁, 邓雪松, 熊书, 李国利, 马强. 去氢木香内酯抑制人肝癌细胞系HepG2增殖及促凋亡[J]. 基础医学与临床, 2020, 40(10): 1369-1373.