自噬相关蛋白LC3Av1在口腔鳞状细胞癌中表达及甲基化对其的影响

口腔医学研究 ›› 2015, Vol. 31 ›› Issue (4): 373-376.

自噬相关蛋白LC3Av1在口腔鳞状细胞癌中表达及甲基化对其的影响

王倩¹, 马金宝^2#, 白桦^1*

1. 大连医科大学口腔医学院口腔内科教研室辽宁大连 116044;
2. 大连医科大学附属第一医院口腔科

收稿日期:2014-09-28 出版日期:2015-04-28 发布日期:2016-04-29
通讯作者: 白桦,E-mail:baihua@dlmedu.edu.cn
作者简介:王倩(1985~ ),女,大连人,助教,硕士,主要从事龋病及牙髓病病因与防治的基础研究。马金宝(1981~ ),男,大连人,主治医师,主要从事口腔临床常见疾病的临床及基础研究。
基金资助:
国家自然科学基金(编号:81300869)

Expression of Autophagy-related Gene LC3Av1 in Oral Squamous Cell Carcinoma and the Effection of Methylation.

WANG Qian, MA Jin-bao, BAI Hua

College of Stomatology, Dalian Medical University, Dalian 116044

Received:2014-09-28 Online:2015-04-28 Published:2016-04-29

摘要/Abstract

摘要： 目的:检测自噬相关基因LC3Av1在口腔鳞状细胞癌中的表达,及甲基化对表达的影响,初步探讨自噬与口腔肿瘤发生的关系。方法:提取18株口腔鳞癌细胞系的总RNA,检测LC3Av1的转录水平表达。并采用COBRA法检测LC3Av1启动子区域CpG岛的甲基化程度。结果:LC3Av1在18株口腔鳞癌中仅有3株表达(表达率为16.7%),而LC3B全部表达。有17株LC3Av1可检测出甲基化。结论:在口腔鳞癌中LC3Av1表达水平降低,提示口腔鳞癌的发生可能与LC3Av1依赖的细胞自噬障碍有关,其表达缺失可能与高甲基化相关。

关键词: 自噬, 口腔鳞状细胞癌, LC3Av1, 甲基化

Abstract: Objective: To detect the expression of autophagy-related gene LC3Av1 in OSCC and the methylation status of LC3Av1, to preliminary discuss the relationship between autophagy and tumorigenesis of OSCC. Methods: The total RNA of 18 OSCC cell lines were extracted and detected LC3Av1 expression at the transcriptional level. Then the methylation status of LC3Av1 transcriptional start site was detected by COBRA. Results: Only 3 cell lines expressed 16.7% in 18 cell lines of OSCC (expressive rate was 16.7%),while LC3B expressed in all lines .And LC3Av1 methylation was detected in 17 cell lines. Conclusion: The expression of LC3Av1 decreased in OSCC suggested that the tumorigenesis of OSCC might relate to obstruction of LC3Av1 dependent autophagy. And the inactivation of LC3Av1 was associated with hypermethylation of LC3Av1 gene.

Key words: Autophagy, OSCC, LC3Av1 , Methylation

中图分类号:

R739.8

王倩, 马金宝, 白桦. 自噬相关蛋白LC3Av1在口腔鳞状细胞癌中表达及甲基化对其的影响[J]. 口腔医学研究, 2015, 31(4): 373-376.

WANG Qian, MA Jin-bao, BAI Hua. Expression of Autophagy-related Gene LC3Av1 in Oral Squamous Cell Carcinoma and the Effection of Methylation.[J]. Journal of Oral Science Research, 2015, 31(4): 373-376.

参考文献

[1] Virgin HW, Levine B. Autophagy genes in immunity [J]. Nat Immunol, 2009, 10(5)∶461-470
[2] Kabeya Y, Mizushima N, Yamamoto A, et al. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation [J]. J Cell Sci, 2004,117(13)∶2805-2812
[3] Wu J, Dang Y, Su W, et al. Molecular cloning and characterization of rat LC3A and LC3B–two novel markers of autophagosome [J]. Biochem Biophys Res Commun, 2006, 339(1)∶437-442
[4] H Bai, J Inoue, T Kawano, et al. A transcriptional variant of the LC3A gene is involved in autophagy and frequently inactivated in human cancers [J]. Oncogene, 2012, 31(40)∶4397-4408
[5] Fleming A, Noda T, Yoshimori T, et al. Chemical modulators of autophagy as biological probes and potential therapeutics [J]. Nat Chem Biol,2011,7(1)∶9-17
[6] Mathew R, Karantza-Wadsworth V, White E. Role of autophagy in cancer [J]. Nat Rev Cancer,2007,7(12)∶961-967
[7] 白宇,全海英,张桐菲,等.顺铂诱导的自噬在口腔鳞癌Tca83细胞中的作用[J].口腔医学研究,2012,28(6)∶566-569
[8] 赵轩一,张泽兵,白宇,等.自噬相关基因Beclinl和MAPlLC3在口腔鳞状细胞癌中的表达及意义[J].口腔医学研究,2012,28(1)∶61-64
[9] 金淑芳,蒋灿华. 细胞自噬相关蛋白8及其连接系统与头颈部恶性肿瘤[J].国际口腔医学杂志,2014,41(2)∶195-198
[10] Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion [J]. Nature, 2008,451(7182)∶1069-1075
[11] Virgin HW, Levine B. Autophagy genes in immunity [J]. Nat Immunol, 2009, 10(5)∶461-470
[12] Takamura A, Komatsu M, Hara T, et al. Autophagy-deficient mice develop multiple liver tumors [J]. Genes Dev,2011,25(8)∶795-800
[13] Yang S, Wang X, Contino G, et al. Pancreatic cancers require autophagy for tumor growth[J]. Genes Dev, 2011, 25(7)∶717-729
[14] Esteller M. Epigenetics in cancer [J]. N Engl J Med, 2008, 358(11)∶1148-1159
[15] Schnekenburger M, Grandjenette C, Ghelfi J, et al. Sustained exposure to the DNA demethylating agent, 2’-deoxy-5-azacytidine, leads to apoptotic cell death in chronic myeloid leukemia by promoting differentiation,senescence, and autophagy [J]. Biochem Pharmacol, 2011, 81(3)∶364-378