山东大学耳鼻喉眼学报 ›› 2023, Vol. 37 ›› Issue (2): 33-38.doi: 10.6040/j.issn.1673-3770.0.2021.542
• 论著 • 上一篇
徐翀,王晓亭,易红良
XU Chong, WANG Xiaoting, YI Hongliang
摘要: 目的 利用单细胞测序技术寻找喉癌细胞糖酵解和谷氨酰胺代谢相关中小分子靶向药物可能的靶基因。 方法 利用R语言对既往单细胞测序的结果重分析,对细胞进行TSNE分类,对代谢相关基因在喉癌各细胞亚群中的表达进行分析。 结果 喉癌细胞糖酵解过程中可能成为小分子代谢药物作用靶点的基因包括:葡萄糖转运蛋白、己糖激酶、丙酮酸激酶;谷氨酰胺分解代谢中可能成为药物作用的靶基因包括:谷氨酰胺转运蛋白、谷氨酰胺酶、谷氨酸脱氢酶1、苹果酸脱氢酶、乳酸脱氢酶、异柠檬酸脱氢酶2。 结论 喉癌细胞中存在与糖酵解和谷氨酰胺代谢相关的基因靶点,可以作为药物研发的方向。
中图分类号:
[1] Chen WQ, Zheng RS, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. doi:10.3322/caac.21338 [2] 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(Pt 2): 228-240. doi:10.1016/j.semcancer.2018.01.008 [3] Barupal DK, Pinkerton KE, Hood C, et al. Environmental tobacco smoke alters metabolic systems in adult rats[J]. Chem Res Toxicol, 2016, 29(11): 1818-1827. doi:10.1021/acs.chemrestox.6b00187 [4] Vanhove K, Graulus GJ, Mesotten L, et al. The metabolic landscape of lung cancer: new insights in a disturbed glucose metabolism[J]. Front Oncol, 2019, 9: 1215. doi:10.3389/fonc.2019.01215 [5] Dang CV. Links between metabolism and cancer[J]. Genes Dev, 2012, 26(9): 877-890. doi:10.1101/gad.189365.112 [6] Vanhove K, Derveaux E, Graulus GJ, et al. Glutamine addiction and therapeutic strategies in lung cancer[J]. Int J Mol Sci, 2019, 20(2): E252. doi:10.3390/ijms20020252 [7] Zhang J, Pavlova NN, Thompson CB. Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine[J]. EMBO J, 2017, 36(10): 1302-1315. doi:10.15252/embj.201696151 [8] Jin L, Alesi GN, Kang S. Glutaminolysis as a target for cancer therapy[J]. Oncogene, 2016, 35(28): 3619-3625. doi:10.1038/onc.2015.447 [9] Wang JB, Erickson JW, Fuji R, et al. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation[J]. Cancer Cell, 2010, 18(3): 207-219. doi:10.1016/j.ccr.2010.08.009 [10] Song L, Zhang S, Yu S, et al. Cellular heterogeneity landscape in laryngeal squamous cell carcinoma[J]. Int J Cancer, 2020, 147(10): 2879-2890. doi:10.1002/ijc.33192 [11] Luo XM, Zhou SH, Fan J. Glucose transporter-1 as a new therapeutic target in laryngeal carcinoma[J]. J Int Med Res, 2010, 38(6): 1885-1892. doi:10.1177/147323001003800601 [12] Shen LF, Zhao X, Zhou SH, et al. In vivo evaluation of the effects of simultaneous inhibition of GLUT-1 and HIF-1α by antisense oligodeoxynucleotides on the radiosensitivity of laryngeal carcinoma using micro 18F-FDG PET/CT[J]. Oncotarget, 2017, 8(21): 34709-34726. doi:10.18632/oncotarget.16671 [13] Patra KC, Wang Q, Bhaskar PT, et al. Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer[J]. Cancer Cell, 2013, 24(2): 213-228. doi:10.1016/j.ccr.2013.06.014 [14] Gao Y, Xu D, Yu G, et al. Overexpression of metabolic markers HK1 and PKM2 contributes to lymphatic metastasis and adverse prognosis in Chinese gastric cancer[J]. Int J Clin Exp Pathol, 2015, 8(8): 9264-9271 [15] Mor I, Cheung EC, Vousden KH. Control of glycolysis through regulation of PFK1: old friends and recent additions[J]. Cold Spring Harb Symp Quant Biol, 2011, 76: 211-216. doi:10.1101/sqb.2011.76.010868 [16] Webb BA, Forouhar F, Szu FE, et al. Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations[J]. Nature, 2015, 523(7558): 111-114. doi:10.1038/nature14405 [17] Lee JH, Liu R, Li J, et al. Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis[J]. Nat Commun, 2017, 8(1): 949. doi:10.1038/s41467-017-00906-9 [18] Dey P, Son JY, Kundu A, et al. Knockdown of pyruvate kinase M2 inhibits cell proliferation, metabolism, and migration in renal cell carcinoma[J]. Int J Mol Sci, 2019, 20(22): E5622. doi:10.3390/ijms20225622 [19] James AD, Richardson DA, Oh IW, et al. Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2(PKM2)[J]. Br J Cancer, 2020, 122(2): 266-278. doi:10.1038/s41416-019-0675-3 [20] Dey P, Kundu A, Sachan, et al. PKM2 knockdown induces autophagic cell death via AKT/mTOR pathway in human prostate cancer cells[J]. Cell Physiol Biochem, 2019, 52(6): 1535-1552. doi:10.33594/000000107 [21] 刘晓晓. PKM2和HIF-1α在喉鳞状细胞癌中的表达及意义[D]. 石家庄: 河北医科大学, 2015. [22] Zhang Z, Liu R, Shuai Y, et al. ASCT2(SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma[J]. Br J Cancer, 2020, 122(1): 82-93. doi:10.1038/s41416-019-0637-9 [23] Lukey MJ, Greene KS, Erickson JW, et al. The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy[J]. Nat Commun, 2016, 7: 11321. doi:10.1038/ncomms11321 [24] Zhang J, Mao S, Guo Y, et al. Inhibition of GLS suppresses proliferation and promotes apoptosis in prostate cancer[J]. Biosci Rep, 2019, 39(6): BSR20181826. doi:10.1042/BSR20181826 [25] Momcilovic M, Bailey ST, Lee JT, et al. Targeted inhibition of EGFR and glutaminase induces metabolic crisis in EGFR mutant lung cancer[J]. Cell Rep, 2017, 18(3): 601-610. doi:10.1016/j.celrep.2016.12.061 [26] Craze ML, El-Ansari R, Aleskandarany MA, et al. Glutamate dehydrogenase(GLUD1)expression in breast cancer[J]. Breast Cancer Res Treat, 2019, 174(1): 79-91. doi:10.1007/s10549-018-5060-z [27] New M, Van Acker T, Sakamaki JI, et al. MDH1 and MPP7 regulate autophagy in pancreatic ductal adenocarcinoma[J]. Cancer Res, 2019, 79(8): 1884-1898. doi:10.1158/0008-5472.CAN-18-2553 [28] Lu YX, Ju HQ, Liu ZX, et al. ME1 regulates NADPH homeostasis to promote gastric cancer growth and metastasis[J]. Cancer Res, 2018, 78(8): 1972-1985. doi:10.1158/0008-5472.CAN-17-3155 [29] Liu C, Cao J, Lin SC, et al. Malic enzyme 1 indicates worse prognosis in breast cancer and promotes metastasis by manipulating reactive oxygen species[J]. Onco Targets Ther, 2020, 13: 8735-8747. doi:10.2147/OTT.S256970 [30] Zhu YH, Gu L, Lin X, et al. Dynamic regulation of ME1 phosphorylation and acetylation affects lipid metabolism and colorectal tumorigenesis[J]. Mol Cell, 2020, 77(1): 138-149.e5. doi:10.1016/j.molcel.2019.10.015 [31] Guo EL, Guo LH, An CM, et al. Prognostic significance of lactate dehydrogenase in patients undergoing surgical resection for laryngeal squamous cell carcinoma[J]. Cancer Control, 2020, 27(1): 1073274820978795. doi:10.1177/1073274820978795 [32] Li JJ, He Y, Tan ZQ, et al. Wild-type IDH2 promotes the Warburg effect and tumor growth through HIF1α in lung cancer[J]. Theranostics, 2018, 8(15): 4050-4061. doi:10.7150/thno.21524 [33] Dang L, Yen K, Attar EC. IDH mutations in cancer and progress toward development of targeted therapeutics[J]. Ann Oncol, 2016, 27(4): 599-608. doi:10.1093/annonc/mdw013 |
[1] | 黄恒丰,马鲲鹏,杨迪,张丽君,张盛林. miR-181b-5P和EPB41L3蛋白在喉癌中的表达及临床意义[J]. 山东大学耳鼻喉眼学报, 2023, 37(1): 41-46. |
[2] | 李利杰,田秀芬. CO2激光联合低温等离子治疗早期声门型喉癌40例[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 79-85. |
[3] | 王媚 李志海. 喉癌干细胞:克服多药耐药性的潜在治疗靶点[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 120-128. |
[4] | 王晓亭,陈正侬,易红良. 利用RNA-seq探讨谷氨酰胺剥夺对喉癌细胞转录组的影响[J]. 山东大学耳鼻喉眼学报, 2022, 36(2): 26-31. |
[5] | 冯成敏,敬一丹,刘海,王冰. 咽喉部鳞状细胞癌细胞系[J]. 山东大学耳鼻喉眼学报, 2021, 35(6): 113-124. |
[6] | 李艳杰, 贾建,杨萍,万保罗. 肿瘤异常蛋白在喉癌临床诊断中的价值研究[J]. 山东大学耳鼻喉眼学报, 2021, 35(5): 70-74. |
[7] | 陈国平,傅敏仪,叶飞,徐建慧. 早期声门型喉癌钬激光与CO2激光手术对比研究[J]. 山东大学耳鼻喉眼学报, 2021, 35(4): 8-11. |
[8] | 吴允刚,张辉,孙聚兴,刘涛,王彩华,杨欣欣,马林祥,李笑颖,庞太忠,李晓瑜. 环甲膜联合喉室入路切除T1B声门型喉癌临床疗效分析[J]. 山东大学耳鼻喉眼学报, 2021, 35(4): 30-34. |
[9] | 石玉琦,佘翠平,张庆丰,刘得龙,焦梦思. 早期声门型喉癌低温等离子射频术后喉部感染诊治经验与教训[J]. 山东大学耳鼻喉眼学报, 2021, 35(4): 129-134. |
[10] | 周恩,肖禹,肖旭平. 等离子射频消融技术在早期声门型喉癌治疗中的应用进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(2): 9-15. |
[11] | 肖旭平,周恩,肖禹. 等离子点状激发射频消融技术治疗早期声门型喉癌(Tis-T1b)31例[J]. 山东大学耳鼻喉眼学报, 2021, 35(2): 60-66. |
[12] | 崔小缓,李丽娜,张延平,蒋兴旺,毕欣欣,冉桃桃,吴莹莹,刘雅莉. 改良负压封闭引流装置在难治性咽瘘治疗中的应用[J]. 山东大学耳鼻喉眼学报, 2020, 34(6): 49-53. |
[13] | 庞振文,黄愉峰,杨爱芳,曾先捷. 喉癌患者术前中性粒细胞/淋巴细胞比值与淋巴结转移的相关性研究[J]. 山东大学耳鼻喉眼学报, 2020, 34(6): 58-62. |
[14] | 谭凤武,邓亚萍,黎可华. 低温等离子射频消融与CO2激光手术治疗早期声门型喉癌疗效的Meta分析[J]. 山东大学耳鼻喉眼学报, 2020, 34(6): 63-71. |
[15] | 徐进敬,胡京华,吴元庆,邓毅,喻唯唯. CO2激光显微手术在喉癌前病变和早期声门型喉癌中的应用[J]. 山东大学耳鼻喉眼学报, 2020, 34(3): 129-133. |
|