鞘氨醇-1-磷酸受体4在口腔鳞状细胞癌中的表达及生物学功能

doi:10.19438/j.cjoms.2024.01.002

中国口腔颌面外科杂志 ›› 2024, Vol. 22 ›› Issue (1): 10-15.doi: 10.19438/j.cjoms.2024.01.002

鞘氨醇-1-磷酸受体4在口腔鳞状细胞癌中的表达及生物学功能

周鑫霞¹，刘敬浩¹，甘桂芳^1#，陈福祥^1,2#

1.上海交通大学医学院附属第九人民医院检验科，上海 200011；
2.上海交通大学医学院医学技术学院，上海 200011

收稿日期:2023-07-21 修回日期:2023-10-23 出版日期:2024-01-20 发布日期:2024-02-05
通讯作者: 陈福祥，E-mail: chenfxsh@163.com；甘桂芳，E-mail: agan1992@126.com。#共同通信作者
作者简介:周鑫霞（1998-），女，在读硕士研究生，E-mail: zxx1282571429@163.com
基金资助:
国家自然科学基金面上项目（81870762）；国家自然科学基金青年项目（82203551）；上海交通大学医工交叉项目（YG2022QN065、JYJC202227）

The expression and biological functions of sphingosine-1-phosphate receptor 4 in oral squamous cell carcinoma

ZHOU Xin-xia¹, LIU Jing-hao¹, GAN Gui-fang¹, CHEN Fu-xiang^1,2

1.Department of Clinical Laboratory, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Shanghai 200011;
2.College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine. Shanghai 200011, China

Received:2023-07-21 Revised:2023-10-23 Online:2024-01-20 Published:2024-02-05

摘要/Abstract

摘要： 目的:探讨鞘氨醇-1-磷酸受体4（sphingosine-1-phosphate receptor 4，S1PR4）在口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）中的表达及生物学功能。方法: 通过实时荧光定量PCR（RT-qPCR）、免疫印迹实验（Western blot）和免疫组织化学染色，分析OSCC组织样本及细胞系（WSU-HN4、WSU-HN6、CAL27、WSU-HN30）中S1PR4的表达。通过S1PR4拮抗剂（CYM50358）抑制S1PR4活性，利用CCK-8以及克隆形成实验检测CYM50358对OSCC细胞增殖的影响。通过流式细胞术分析CYM500358对OSCC细胞凋亡的影响。采用SPSS 23.0软件包对数据进行统计学分析。结果: OSCC中的S1PR4 转录及表达显著上调，CYM50358处理组OSCC细胞增殖活性显著低于空白对照组（P<0.05），CYM50358处理组OSCC细胞克隆形成能力显著低于空白对照组（P<0.05），CYM50358处理组OSCC细胞凋亡比例显著高于空白对照组（P<0.05）。结论: S1PR4在OSCC中表达上调，S1PR4拮抗剂可抑制OSCC细胞生长并促进细胞凋亡，或为OSCC的治疗提供新的潜在靶点。

关键词: 口腔鳞状细胞癌, 鞘氨醇-1-磷酸受体4（S1PR4）, 生物学功能, 细胞凋亡

Abstract: PURPOSE: To explore the expression and biological functions of sphingosine-1-phosphate receptor 4 (S1PR4) in oral squamous cell carcinoma (OSCC). METHODS: The expression of S1PR4 in OSCC tissue samples and cell lines (WSU-HN4, WSU-HN6, CAL27, WSU-HN30) was analyzed by RT-qPCR, Western blot and IHC. The activity of S1PR4 was inhibited by S1PR4 antagonist(CYM50358), and the effect of CYM50358 on proliferation of OSCC cells was detected by CCK-8 and clonal formation assay. The effect of CYM500358 on apoptosis of OSCC cells was evaluated by flow cytometry. SPSS 23.0 software package was used for statistical analysis. RESULTS: The transcription and expression of S1PR4 were up-regulated in OSCC. The activity of proliferation and clonality were decreased(P<0.05), while the percentage of apoptotic cells was increased in CYM50358-treated OSCC cells(P<0.05). CONCLUSIONS: The expression of S1PR4 is up-regulated in OSCC. S1PR4 antagonist can significantly reduce viability and promote apoptosis of OSCC cells, and may be a potential indicator for treatment of OSCC.

Key words: Oral squamous cell carcinoma, OSCC, Sphingosine-1-phosphate receptor 4(S1PR4), Biological function, Apoptosis

中图分类号:

R739.8

周鑫霞，刘敬浩，甘桂芳，陈福祥. 鞘氨醇-1-磷酸受体4在口腔鳞状细胞癌中的表达及生物学功能[J]. 中国口腔颌面外科杂志, 2024, 22(1): 10-15.

ZHOU Xin-xia, LIU Jing-hao, GAN Gui-fang, CHEN Fu-xiang. The expression and biological functions of sphingosine-1-phosphate receptor 4 in oral squamous cell carcinoma[J]. China J Oral Maxillofac Surg, 2024, 22(1): 10-15.

参考文献

[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] Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma[J]. Nat Rev Dis Primers, 2020, 6(1): 92-141.
[3] Blatt S, Krüger M, Ziebart T, et al. Biomarkers in diagnosis and therapy of oral squamous cell carcinoma: a review of the literature[J]. J Craniomaxillofac Surg, 2017, 45(5): 722-730.
[4] Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma-an update: oral & oropharyngeal cancer update[J]. CA Cancer J Clin, 2015, 65(5): 401-421.
[5] Ogretmen B. Sphingolipid metabolism in cancer signalling and therapy[J]. Nat Rev Cancer, 2018, 18(1):33-50.
[6] Roi A, Roi CI, Negru?iu ML, et al. The challenges of OSCC diagnosis: salivary cytokines as potential biomarkers[J]. J Clin Med, 2020, 9(9): 2866.
[7] Shrestha AD, Vedsted P, Kallestrup P, et al. Prevalence and incidence of oral cancer in low- and middle-income countries: a scoping review[J]. Eur J Cancer Care (Engl), 2020,29(2): e13207.
[8] Du Y, Peyser ND, Grandis JR. Integration of molecular targeted therapy with radiation in head and neck cancer[J]. Pharmacol Ther, 2014, 142(1): 88-98.
[9] Chun J, Hla T, Lynch KR, et al. International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature[J]. Pharmacol Rev, 2010,62(4):579-587.
[10] Liu S, Ni C, Zhang D, et al. S1PR1 regulates the switch of two angiogenic modes by VE-cadherin phosphorylation in breast cancer[J]. Cell Death Dis, 2019, 10(3): 200-215.
[11] Anu B, Namitha NN, Harikumar KB. S1PR1 signaling in cancer: a current perspective[J]. Adv Protein Chem Struct Biol, 2021, 125: 259-274.
[12] Shen Y, Zhao S, Wang S, et al. S1P/S1PR3 axis promotes aerobic glycolysis by YAP/c-MYC/PGAM1 axis in osteosarcoma[J]. EBioMedicine, 2019, 40: 210-223.
[13] Wang W, Hind T, Lam BWS, et al. Sphingosine 1-phosphate signaling induces SNAI2 expression to promote cell invasion in breast cancer cells[J]. FASEB J, 2019, 33(6): 7180-7191.
[14] Zhao J, Liu J, Lee JF, et al. TGF-β/SMAD3 pathway stimulates sphingosine-1 phosphate receptor 3 expression: implication of sphingosine-1 phosphate receptor 3 in lung adenocarcinoma progression[J]. J Biol Chem, 2016,291(53): 27343-27353.
[15] Sarkar J, Aoki H, Wu R, et al. Conjugated bile acids accelerate progression of pancreatic cancer metastasis via S1PR2 signaling in cholestasis[J]. Ann Surg Oncol, 2023, 30(3): 1630-1641.
[16] Yamashita H, Kitayama J, Shida D, et al. Sphingosine 1-phosphate receptor expression profile in human gastric cancer cells: differential regulation on the migration and proliferation[J]. J Surg Res, 2006, 130(1): 80-87.
[17] Petti L, Rizzo G, Rubbino F, et al. Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer[J]. J Exp Clin Cancer Res, 2020, 39(1): 253-267.
[18] Ohotski J, Rosen H, Bittman R,et al. Sphingosine kinase 2 prevents the nuclear translocation of sphingosine 1-phosphate receptor-2 and tyrosine 416 phosphorylated c-Src and increases estrogen receptor negative MDA-MB-231 breast cancer cell growth: the role of sphingosine 1-phosphate receptor-4[J]. Cell Signal, 2014, 26(5): 1040-1047.
[19] Cartier A, Hla T. Sphingosine 1-phosphate: lipid signaling in pathology and therapy[J]. Science, 2019,366(6463): eaar5551.
[20] Brinkmann V, Billich A, Baumruker T, et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis[J]. Nat Rev Drug Discov, 2010, 9(11): 883-897.
[21] Gaber T.Siponimod for active secondary progressive multiple sclerosis[J]. Prog Neurol Psychiatry, 2021, 25(2): 4-5.
[22] Blanco R, Martínez-Navarrete G, Valiente-Soriano FJ, et al. The S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell loss[J]. Exp Eye Res, 2017, 164: 37-45.
[23] Weske S, Vaidya M, Von Wnuck Lipinski K, et al. Agonist-induced activation of the S1P receptor 2 constitutes a novel osteoanabolic therapy for the treatment of osteoporosis in mice[J]. Bone, 2019, 125(1): 1-7.
[24] Li MH, Swenson R, Harel M, et al. Antitumor activity of a novel sphingosine-1-phosphate 2 antagonist, AB1, in neuroblastoma[J]. J Pharmacol Exp Ther, 2015, 354(3): 261-268.
[25] Onuma T, Tanabe K, Kito Y, et al. Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor[J]. Thrombosis Res, 2017, 156(1): 91-100.
[26] Salomone S, Waeber C. Selectivity and specificity of sphingosine-1-phosphate receptor ligands: caveats and critical thinking in characterizing receptor-mediated effects[J]. Front Pharmacol, 2011, 2(1): 9-16.
[27] Gergely P, Nuesslein-Hildesheim B, Guerini D, et al. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate[J]. Br J Pharmacol, 2012, 167(5): 1035-1047.

鞘氨醇-1-磷酸受体4在口腔鳞状细胞癌中的表达及生物学功能

The expression and biological functions of sphingosine-1-phosphate receptor 4 in oral squamous cell carcinoma

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	孙晓梅, 段晓峰. 去泛素化酶在口腔鳞癌中的研究进展[J]. 中国口腔颌面外科杂志, 2024, 22(3): 294-299.
[2]	李锦存, 翟堃, 胡晨, 刘絮影, 马兴平, 马坚. 整合WGNCA和PPI网络鉴定口腔鳞状细胞癌的关键基因[J]. 中国口腔颌面外科杂志, 2024, 22(2): 128-136.
[3]	韩林孜, 周建华, 董磊, 赵璐, 袁荣涛. 肿瘤相关成纤维细胞对口腔鳞状细胞癌生物学行为影响的研究进展[J]. 中国口腔颌面外科杂志, 2024, 22(1): 84-91.
[4]	李贵忠, 李洁莹, 周凯, 孟宇翔, 王可心, 葛胜优, 宋凯, 冯元勇, 陶月琴, 展晓红, 尚伟. 淋巴结外扩展对口腔鳞癌患者TNM分期及生存预后的影响[J]. 中国口腔颌面外科杂志, 2023, 21(4): 377-383.
[5]	热孜万姑丽·亚森, 买热拍提·买明, 李晨曦, 龚忠诚. 牙龈卟啉单胞菌促进口腔鳞状细胞癌进展的作用及机制研究进展[J]. 中国口腔颌面外科杂志, 2023, 21(2): 186-190.
[6]	兰嵘, 阮敏, 韩楠男, 王凤. 左下种植修复后发生植体周围鳞状细胞癌1例报告[J]. 中国口腔颌面外科杂志, 2023, 21(2): 203-205.
[7]	苏姿尚, 崔文丽, 张梦云, 姚志涛. 口腔鳞状细胞癌患者颈部淋巴结特征与预后的关系[J]. 中国口腔颌面外科杂志, 2023, 21(1): 41-48.
[8]	陈正岗, 王奇民, 童磊, 王云英, 徐晓娜, 王莹, 韩红钰, 盛善桂, 王少如. 沉默Icmt基因对舌鳞癌CAL-27和SCC-4细胞增殖、凋亡及细胞周期的影响[J]. 中国口腔颌面外科杂志, 2021, 19(2): 97-104.
[9]	陈秀敏, 刘族志, 林建能. 血浆miR-136-5p表达水平对口腔鳞状细胞癌患者预后预测的价值[J]. 中国口腔颌面外科杂志, 2020, 18(6): 526-530.
[10]	梁思源, 赵铜超, 周知航, 琚梧桐, 刘莹, 张志愿, 钟来平. 可利霉素对口腔鳞癌细胞生物学活性的影响[J]. 中国口腔颌面外科杂志, 2020, 18(4): 308-313.
[11]	王锋, 李翔, 王宇帆, 杨宏宇. 环状RNA在口腔鳞状细胞癌中的作用探讨[J]. 中国口腔颌面外科杂志, 2019, 17(6): 496-502.
[12]	李翔, 苏文, 张寒雨, 张璧茹, 杨宏宇. 沉默环状RNA hsa_circ_0006677 表达对口腔鳞状细胞癌迁移及侵袭能力的影响[J]. 中国口腔颌面外科杂志, 2019, 17(4): 289-294.
[13]	朱东旺, 孙文文, 赵铜超, 钟来平, 张陈平, 张志愿. 人口腔鳞状细胞癌细胞系TSCC2016的建立及生物学特性分析[J]. 中国口腔颌面外科杂志, 2019, 17(3): 204-209.
[14]	马利, 石冰, 张东升, 郑谦. 细胞凋亡及上皮-间充质转化在腭胚突融合过程中的作用探讨[J]. 中国口腔颌面外科杂志, 2018, 16(6): 493-497.
[15]	魏立, 周琦, 江莉婷, 李宁, 高益鸣. 利塞膦酸钠对骨质疏松大鼠牙槽骨Bcl-2、BAX表达的影响[J]. 中国口腔颌面外科杂志, 2018, 16(5): 402-408.