蛋白质赖氨酸甲基转移酶在甲状腺癌中的研究进展

doi:10.16139/j.1007-9610.2023.06.013

摘要/Abstract

摘要：

蛋白质赖氨酸甲基转移酶（protein lysine methyltransferase, PKMT）能催化组蛋白尾部和非组蛋白靶标上的赖氨酸残基甲基化。这类重要的翻译后修饰，可影响染色质的结构和紧密程度，进而影响基因表达。越来越多证据表明，PKMT的遗传改变会影响PKMT在组织中的正常表达从而发挥致癌或抑癌功能。在多种实体瘤中发现PKMT的表达与肿瘤病人的预后有关。本综述总结Zeste增强子同源物2（enhancer of zeste homologue 2, EZH2）、组蛋白-赖氨酸N-甲基转移酶2（histone-lysine N-methyltransferase 2, KMT2）家族和含有SET结构域及MYND结构域蛋白（SET and MYND domain-containing protein, SMYD）家族三类主要PKMT的功能及其在甲状腺癌中的作用。

关键词: 蛋白质赖氨酸甲基转移酶(PRMT), 甲状腺癌, Zeste增强子同源物2(EZH2), 组蛋白-赖氨酸N-甲基转移酶2(KMT2)家族, 含有SET结构域及MYND结构域蛋白(SMYD)家族

Abstract:

Protein lysine methyltransferases (PKMT) catalyze methylation of lysine residues on histone tails and non-histone targets. These important post-translational modifications affect the structure and compactness of chromatin, which in turn affects gene expression. There is growing evidence that genetic alterations in PKMT affect the normal expression of PKMT in tissues and thus exert oncogenic or tumor suppressor functions. The expression of PKMT has been found to be associated with the prognosis of tumor patients in a variety of solid tumors. In this review, we summarized the functions of three major PKMT, including EZH2, KMT2 family and SMYD family, and their roles in thyroid carcinoma.

Key words: Protein lysine methyltransferase(PRMT), Thyroid carcinoma, Enhancer of zeste homologue 2(EZH2), Histone-lysine N-methyltransferase 2(KMT2) family, SET and MYND domain-containing protein(SMYD) family

中图分类号:

R736.1

何熹, 史苑, 钱凯, 王卓颖. 蛋白质赖氨酸甲基转移酶在甲状腺癌中的研究进展[J]. 外科理论与实践, 2023, 28(06): 563-567.

HE Xi, SHI Yuan, QIAN Kai, WANG Zhuoying. Advances of protein lysine methyltransferases in thyroid carcinoma[J]. Journal of Surgery Concepts & Practice, 2023, 28(06): 563-567.

参考文献 37

[1]	SUNG H, FERLAY J, SIEGEL R L, 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. doi: 10.3322/caac.v71.3 URL
[2]	ZHENG R S, ZHANG S W, ZENG HW, et al. Cancer incidence and mortality in China, 2016[J]. J National Cancer Center, 2022, 2(1):1-9. doi: 10.1016/j.jncc.2022.02.002 URL
[3]	DAWSON M A, KOUZARIDES T. Cancer epigenetics: from mechanism to therapy[J]. Cell, 2012, 150(1):12-27. doi: 10.1016/j.cell.2012.06.013 pmid: 22770212
[4]	BHATTACHARYYA S, MATTIROLI F, LUGER K. Archaeal DNA on the histone merry-go-round[J]. FEBS J, 2018, 285(17):3168-3174. doi: 10.1111/febs.14495 pmid: 29729078
[5]	BAE W K, HENNIGHAUSEN L. Canonical and non-canonical roles of the histone methyltransferase EZH2 in mammary development and cancer[J]. Mol Cell Endocrinol, 2014, 382(1):593-597. doi: S0303-7207(13)00205-0 pmid: 23684884
[6]	BORBONE E, TRONCONE G, FERRARO A, et al. Enhancer of zeste homolog 2 overexpression has a role in the development of anaplastic thyroid carcinomas[J]. J Clin Endocrinol Metab, 2011, 96(4):1029-1038. doi: 10.1210/jc.2010-1784 pmid: 21289264
[7]	GUO K, QIAN K, SHI Y, et al. LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p[J]. Cell Death Dis, 2021, 12(12):1097. doi: 10.1038/s41419-021-04386-0 pmid: 34811354
[8]	XUE L, YAN H, CHEN Y, et al. EZH2 upregulation by ERα induces proliferation and migration of papillary thyroid carcinoma[J]. BMC Cancer, 2019, 19(1):1094. doi: 10.1186/s12885-019-6306-9 pmid: 31718595
[9]	SPONZIELLO M, DURANTE C, BOICHARD A, et al. Epigenetic-related gene expression profile in medullary thyroid cancer revealed the overexpression of the histone methyltransferases EZH2 and SMYD3 in aggressive tumours[J]. Mol Cell Endocrinol, 2014, 392(1-2):8-13. doi: 10.1016/j.mce.2014.04.016 pmid: 24813658
[10]	TSAI C C, CHIEN M N, CHANG Y C, et al. Overexpression of histone H3 lysine 27 trimethylation is associated with aggressiveness and dedifferentiation of thyroid cancer[J]. Endocr Pathol, 2019, 30(4):305-311. doi: 10.1007/s12022-019-09586-1
[11]	WANG Z, DAI J, YAN J, et al. Targeting EZH2 as a novel therapeutic strategy for sorafenib-resistant thyroid carcinoma[J]. J Cell Mol Med, 2019, 23(7):4770-4778. doi: 10.1111/jcmm.14365 pmid: 31087496
[12]	DE MELLO D C, SAITO K C, CRISTOVÃO M M, et al. Modulation of EZH2 activity induces an antitumoral effect and cell redifferentiation in anaplastic thyroid cancer[J]. Int J Mol Sci, 2023, 24(9):7872. doi: 10.3390/ijms24097872 URL
[13]	梁碧君, 李湘平, 鲁娟, 等. EZH2对鼻咽癌细胞增殖和侵袭影响的研究[J]. 中华耳鼻咽喉头颈外科杂志, 2012, 47(4):298-304.
	LIANG B J, LI X P, LU J, et al. Study on the effect of EZH2 on the proliferation and invasion of nasopharyngeal cancer cells[J]. Chin J Otorhinolaryngol Head Neck Surg, 2012, 47(4):298-304.
[14]	SI Y, WEN J, HU C, et al. LINC00891 promotes tumorigenesis and metastasis of thyroid cancer by regulating SMAD2/3 via EZH2[J]. Curr Med Chem, 2023.
[15]	DE MARTINO M, PELLECCHIA S, DECAUSSIN-PETRUCCI M, et al. Drug-induced inhibition of HMGA and EZH2 activity as a possible therapy for anaplastic thyroid carcinoma[J]. Cell Cycle, 2024:1-14.
[16]	ZHANG C, HUA Y, QIU H, et al. KMT2A regulates cervical cancer cell growth through targeting VDAC1[J]. Aging (Albany NY), 2020, 12(10):9604-9620.
[17]	ZHAO D, YUAN H, FANG Y, et al. Histone methyltransferase KMT2B promotes metastasis and angiogenesis of cervical cancer by upregulating EGF expression[J]. Int J Biol Sci, 2023, 19(1):34-49. doi: 10.7150/ijbs.72381 pmid: 36594087
[18]	FENG J F, WANG J, XIE G, et al. KMT2B promotes the growth of renal cell carcinoma via upregulation of SNHG12 expression and promotion of CEP55 transcription[J]. Cancer Cell Int, 2022, 22(1):197. doi: 10.1186/s12935-022-02607-w
[19]	SIERRA J, YOSHIDA T, JOAZEIRO C A, et al. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes[J]. Genes Dev, 2006, 20(5):586-600. doi: 10.1101/gad.1385806 URL
[20]	COLAMAIO M, PUCA F, RAGOZZINO E, et al. MiR-142-3p down-regulation contributes to thyroid follicular tumorigenesis by targeting ASH1L and MLL1[J]. J Clin Endocrinol Metab, 2015, 100(1):E59-E69. doi: 10.1210/jc.2014-2280 URL
[21]	FAGAN R J, DINGWALL A K. COMPASS ascending: emerging clues regarding the roles of MLL3/KMT2C and MLL2/KMT2D proteins in cancer[J]. Cancer Lett, 2019, 458:56-65. doi: S0304-3835(19)30319-2 pmid: 31128216
[22]	NA F, PAN X, CHEN J, et al. KMT2C deficiency promotes small cell lung cancer metastasis through DNMT3A-mediated epigenetic reprogramming[J]. Nat Cancer, 2022, 3(6):753-767. doi: 10.1038/s43018-022-00361-6
[23]	ALAM H, TANG M, MAITITUOHETI M, et al. KMT2D deficiency impairs super-enhancers to confer a glycolytic vulnerability in lung cancer[J]. Cancer Cell, 2020, 37(4):599-617.e7. doi: S1535-6108(20)30106-9 pmid: 32243837
[24]	CHO S J, YOON C, LEE J H, et al. KMT2C mutations in diffuse-type gastric adenocarcinoma promote epithelial-to-mesenchymal transition[J]. Clin Cancer Res, 2018, 24(24):6556-6569. doi: 10.1158/1078-0432.CCR-17-1679 URL
[25]	NIEMINEN T T, WALKER C J, OLKINUORA A, et al. Thyroid carcinomas that occur in familial adenomatous polyposis patients recurrently harbor somatic variants in APC, BRAF, and KTM2D[J]. Thyroid, 2020, 30(3):380-388. doi: 10.1089/thy.2019.0561 URL
[26]	SONG J, LIU Y, CHEN Q, et al. Expression patterns and the prognostic value of the SMYD family members in human breast carcinoma using integrative bioinformatics analysis[J]. Oncol Lett, 2019, 17(4):3851-3861. doi: 10.3892/ol.2019.10054 pmid: 30930987
[27]	KOMATSU S, ICHIKAWA D, HIRAJIMA S, et al. Overexpression of SMYD2 contributes to malignant outcome in gastric cancer[J]. Br J Cancer, 2015, 112(2):357-364. doi: 10.1038/bjc.2014.543
[28]	XU W, CHEN F, FEI X, et al. Overexpression of SET and MYND domain-containing protein 2 (SMYD2) is associated with tumor progression and poor prognosis in patients with papillary thyroid carcinoma[J]. Med Sci Monit, 2018, 24:7357-7365. doi: 10.12659/MSM.910168 URL
[29]	HUANG J, PEREZ-BURGOS L, PLACEK B J, et al. Repression of p53 activity by Smyd2-mediated methylation[J]. Nature, 2006, 444(7119):629-632. doi: 10.1038/nature05287
[30]	TANG M, CHEN G, TU B, et al. SMYD2 inhibition-mediated hypomethylation of Ku70 contributes to impaired nonhomologous end joining repair and antitumor immunity[J]. Sci Adv, 2023, 9(24):eade6624. doi: 10.1126/sciadv.ade6624 URL
[31]	HAMAMOTO R, SILVA F P, TSUGE M, et al. Enhanced SMYD3 expression is essential for the growth of breast cancer cells[J]. Cancer Sci, 2006, 97(2):113-118. doi: 10.1111/cas.2006.97.issue-2 URL
[32]	ZHU Y, ZHU M X, ZHANG X D, et al. SMYD3 stimulates EZR and LOXL2 transcription to enhance proliferation, migration, and invasion in esophageal squamous cell carcinoma[J]. Hum Pathol, 2016, 52:153-163. doi: 10.1016/j.humpath.2016.01.012 pmid: 26980013
[33]	KUNIZAKI M, HAMAMOTO R, SILVA F P, et al. The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3[J]. Cancer Res, 2007, 67(22):10759-10765. doi: 10.1158/0008-5472.CAN-07-1132 pmid: 18006819
[34]	RUBIO-TOMÁS T. Novel insights into SMYD2 and SMYD3 inhibitors: from potential anti-tumoural therapy to a variety of new applications[J]. Mol Biol Rep, 2021, 48(11):7499-7508. doi: 10.1007/s11033-021-06701-6
[35]	SHANG L, WEI M. Inhibition of SMYD2 sensitized cisplatin to resistant cells in NSCLC through activating p53 pathway[J]. Front Oncol, 2019, 9:306. doi: 10.3389/fonc.2019.00306 pmid: 31106145
[36]	FAN Y, FAN X, YAN H, et al. Long non-coding ROR promotes the progression of papillary thyroid carcinoma through regulation of the TESC/ALDH1A1/TUBB3/PTEN axis[J]. Cell Death Dis, 2022, 13(2):157. doi: 10.1038/s41419-021-04210-9 pmid: 35173149
[37]	LIAO T, WANG Y J, HU J Q, et al. Histone methyltransferase KMT5A gene modulates oncogenesis and lipid metabolism of papillary thyroid cancer in vitro[J]. Oncol Rep, 2018, 39(5):2185-2192.