线粒体拓扑异构酶Ⅰ在头颈鳞癌中的表达及意义

doi:10.19438/j.cjoms.2023.05.003

中国口腔颌面外科杂志 ›› 2023, Vol. 21 ›› Issue (5): 439-445.doi: 10.19438/j.cjoms.2023.05.003

线粒体拓扑异构酶Ⅰ在头颈鳞癌中的表达及意义

翟培淞^1,*, 童桐^2,*, 刘纯¹, 马海龙^1#, 张建军^1#

1.上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室, 上海市口腔医学研究所,上海市头颈肿瘤诊治和转化研究中心,上海 200011;
2.上海市口腔医院口腔颌面外科,上海市颅颌面发育与疾病重点实验室,上海 200001

收稿日期:2023-05-19 修回日期:2023-07-17 出版日期:2023-09-20 发布日期:2023-10-11
通讯作者: 马海龙,E-mail:mahl21@sjtu.edu.cn;张建军,E-mail: zjjbio@sjtu.edu.cn。^#共同通信作者
作者简介:翟培淞（1997-）,男,在读硕士研究生,E-mail: ps_zhai@126.com;童桐（1996-）,女,硕士,E-mail:1605049815@qq.com。^*并列第一作者
基金资助:
国家自然科学基金（82272983,82173148）

The impact of mitochondrial topoisomerase I expression in head and neck squamous cell carcinoma

ZHAI Pei-song¹, TONG Tong², LIU Chun¹, MA Hai-long¹, ZHANG Jian-jun¹

1. Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology; Shanghai Center of Head and Neck Oncology Clinical and Translational Science. Shanghai 200011;
2. Department of Oromaxillofacial Surgery, Shanghai Stomatological Hospital & School of Stomatology, Fudan University; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University. Shanghai 200001, China

Received:2023-05-19 Revised:2023-07-17 Online:2023-09-20 Published:2023-10-11

摘要/Abstract

摘要： 目的：分析线粒体拓扑异构酶Ⅰ（mitochondrial topoisomerase I,TOP1MT）与头颈鳞癌（head and neck squamous cell carcinoma,HNSCC）临床病理特征的相关性,探讨其对HNSCC顺铂耐药的影响。方法：分析83例HNSCC患者的临床病理信息,综合免疫组织化学染色和实时荧光定量PCR（qRT-PCR）结果,分析TOP1MT是否与化疗耐药等临床病理特征相关。通过体外实验,分析在顺铂作用下,TOP1MT对HNSCC细胞药物敏感性、增殖和迁移能力的影响。采用SPSS 26.0软件包对数据进行统计学分析。结果：高表达TOP1MT与HNSCC患者的肿瘤大小、临床分期、生存期、TPF方案敏感度和不良预后相关,TOP1MT高表达的患者,生存期显著低于中表达和低表达患者。体外实验表明,TOP1MT促进HNSCC细胞的顺铂耐药,在20 μmol/L顺铂作用下,过表达TOP1MT显著促进了HNSCC细胞的迁移和增殖能力。结论：TOP1MT高表达促进HNSCC恶性进展及顺铂治疗抵抗,为HNSCC的临床治疗提供了新的潜在靶点。

关键词: 线粒体拓扑异构酶Ⅰ, 头颈鳞癌, 顺铂, 化疗耐药

Abstract: PURPOSE: To analyze the correlation between mitochondrial topoisomerase I (TOP1MT) and the clinicopathological characteristics of head and neck squamous cell carcinoma(HNSCC), and to explore its impact on cisplatin resistance in HNSCC. METHODS: The correlation between TOP1MT and clinicopathological characteristics was analyzed by combining the information of 83 clinical patients with the results of immunohistochemical staining and real-time fluorescence quantitative PCR(qRT-PCR). The effect of TOP1MT on proliferation and migration of HNSCC cells with cisplatin treatment was analyzed by in vitro experiments. SPSS 26.0 software package was used for statistical analysis. RESULTS: High expressed TOP1MT was related to tumor size, clinical stage, overall survival, efficacy of TPF regimen, and worse prognosis of HNSCC patients, and the survival probability of patients with high expression of TOP1MT was significantly lower than that of patients with moderate and low expression. In vitro experiments showed that overexpression of TOP1MT significantly promoted the migration and proliferation of HNSCC cells HN30 and HN4 with 20 μmol/L cisplatin treatment. CONCLUSIONS: High expression of TOP1MT in HNSCC indicates insensitivity to chemotherapy and decreased overall survival. The experiment confirmed that TOP1MT promotes HNSCC development and may act as a potential target for clinical therapy.

Key words: TOP1MT, Head and neck squamous cell carcinoma, Cisplatin, Chemoresistance

中图分类号:

R739.8

翟培淞, 童桐, 刘纯, 马海龙, 张建军. 线粒体拓扑异构酶Ⅰ在头颈鳞癌中的表达及意义[J]. 中国口腔颌面外科杂志, 2023, 21(5): 439-445.

ZHAI Pei-song, TONG Tong, LIU Chun, MA Hai-long, ZHANG Jian-jun. The impact of mitochondrial topoisomerase I expression in head and neck squamous cell carcinoma[J]. China J Oral Maxillofac Surg, 2023, 21(5): 439-445.

参考文献

[1] Solomon B, Young RJ, Rischin D.Head and neck squamous cell carcinoma: genomics and emerging biomarkers for immunomodulatory cancer treatments[J]. Semin Cancer Biol, 2018, 52(2): 228-240.
[2] Smith CD, Carmeli S, Moore RE, et al.Scytophycins, novel microfilament-depolymerizing agents which circumvent P-glycoprotein-mediated multidrug resistance[J]. Cancer Res, 1993, 53(6): 1343-1347.
[3] Sakamoto M, Kondo A, Kawasaki K, et al.Analysis of gene expression profiles associated with cisplatin resistance in human ovarian cancer cell lines and tissues using cDNA microarray[J]. Human Cell, 2001, 14(4): 305-315.
[4] Kasahara K, Fujiwara Y, Nishio K, et al.Metallothionein content correlates with the sensitivity of human small cell lung cancer cell lines to cisplatin[J]. Cancer Res, 1991,51(12):3237-3242.
[5] Chaney SG, Sancar A.DNA repair: enzymatic mechanisms and relevance to drug response[J]. J Natl Cancer Inst, 1996, 88(19):1346-1360.
[6] Vousden KH, Lane DP.P53 in health and disease[J]. Nat Rev Mol Cell Biol, 2007, 8(4): 275-283.
[7] Hengstler JG, Pilch H, Schmidt M, et al.Metallothionein expression in ovarian cancer in relation to histopathological parameters and molecular markers of prognosis[J]. Int J Cancer, 2001, 95(2): 121-127.
[8] Tong T, Qin X, Jiang Y, et al.A novel CREB5/TOP1MT axis confers cisplatin resistance through inhibiting mitochondrial apoptosis in head and neck squamous cell carcinoma[J]. BMC Med, 2022, 20(1):1-21.
[9] Lee NCJ, Kelly JR, Park HS, et al.Patterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma[J]. Oral Oncol, 2018, 85: 35-39.
[10] Theile D, Ketabi-Kiyanvash N, Herold-Mende C, et al.Evaluation of drug transporters’ significance for multidrug resistance in head and neck squamous cell carcinoma[J]. Head and Neck, 2011, 33(7): 959-968.
[11] Galluzzi L, Senovilla L, Vitale I, et al.Molecular mechanisms of cisplatin resistance[J]. Oncogene, 2012, 31(15): 1869-1883.
[12] Pommier Y, Nussenzweig A, Takeda S, et al.Human topoisomerases and their roles in genome stability and organization[J]. Nat Rev Mol Cell Biol, 2022, 23(6): 407-427.
[13] Baechler SA, Factor VM, Rosa ID, et al.The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis[J]. Nat Commun, 2019, 10(1): 1-13.
[14] Stewart L, Stewart L, Redinbo MR, et al.A model for the mechanism of human topoisomerase I[J]. Science, 1998, 279(5356): 1534-1541.
[15] Fei L, Lu Z, Xu Y, et al.A comprehensive pan-cancer analysis of the expression characteristics, prognostic value, and immune characteristics of TOP1MT[J]. Front Genet, 2022, 13: 920897.
[16] Zoppoli G, Douarre C, Rosa ID, et al.Coordinated regulation of mitochondrial topoisomerase IB with mitochondrial nuclear encoded genes and MYC[J]. Nucleic Acids Res, 2011, 39(15): 6620-6632.
[17] Khiati S, Rosa ID, Sourbier C, et al.Mitochondrial topoisomerase I ( Top1mt ) is a novel limiting factor of doxorubicin cardiotoxicity[J]. Clin Cancer Res, 2014, 20(18): 4873-4881.
[18] Lu Q, Wang M, Gui Y, et al.Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis[J]. Cell Death Dis, 2020, 11(5): 364-378.
[19] Yu X, Meng X, Xu M, et al.Celastrol ameliorates cisplatin nephrotoxicity by inhibiting NF-κB and improving mitochondrial function[J]. EBioMedicine, 2018, 36: 266-280.
[20] Gong W, Lu L, Zhou Y, et al.The novel STING antagonist H151 ameliorates cisplatin-induced acute kidney injury and mitochondrial dysfunction[J]. Am J Physiol Renal Physiol, 2021, 320(4): F608-F616.
[21] Bajwa A, Rosin DL, Chroscicki P, et al.Sphingosine 1-phosphate receptor-1 enhances mitochondrial function and reduces cisplatin-induced tubule injury[J]. J Am Soc Nephrol, 2015, 26(4): 908-925.
[22] Kohno K, Wang KY, Takahashi M, et al.Mitochondrial transcription factor a and mitochondrial genome as molecular targets for cisplatin-based cancer chemotherapy[J]. Int J Mol Sci, 2015, 16(8): 19836-19850.

线粒体拓扑异构酶Ⅰ在头颈鳞癌中的表达及意义

The impact of mitochondrial topoisomerase I expression in head and neck squamous cell carcinoma

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