Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2021, Vol. 35 ›› Issue (1): 125-130.doi: 10.6040/j.issn.1673-3770.0.2020.102

Previous Articles    

Research progress on the relationship between the C2H2 zinc finger protein family and laryngeal cancer

LI WenjingOverview,LIU MingGuidance   

  1. Department of Otorhinolaryngology & Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, China
  • Published:2021-02-01

Abstract: Laryngeal cancer is one of the most common malignancies in head and neck cancer. Although continuous progress is being made in the diagnosis and treatment of laryngeal cancer, patient survival rates have not greatly improved. Cysteine-2/histidine-2(C2H2)-type zinc finger proteins(ZNFs), the largest family of transcription factors in humans, are characterized by multiple tandemly arranged zinc fingers. C2H2-type ZNFs are involved in normal biological processes such as transcriptional regulation, organ and tissue development, and differentiation; however, they are also associated with the occurrence and development of cancer. Studies have shown that the abnormal expression of various C2H2-type ZNFs is closely related to the clinicopathologic features and prognosis of cancers. This paper primarily reviews the progress of research on the relationship between C2H2-type ZNFs and laryngeal cancer.

Key words: Laryngeal cancer, C2H2-type zinc finger proteins, Tumor growth, Tumor suppression

CLC Number: 

  • R739
[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. doi:10.3322/caac.21492.
[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020[J]. CA A Cancer J Clin, 2020, 70(1): 7-30. doi:10.3322/caac.21590.
[3] 中华耳鼻咽喉头颈外科杂志编辑委员会头颈外科组, 中华医学会耳鼻咽喉头颈外科学分会头颈学组, 李晓明. 喉癌外科手术及综合治疗专家共识[J]. 中华耳鼻咽喉头颈外科杂志, 2014, 49(8): 620-626. doi:10.3760/cma.j.issn.1673-0860.2014.08.002.
[4] 孙笑晗,李娜. 喉保留策略在喉癌治疗中的应用—美国临床肿瘤学会临床实践指南更新(2017)介绍[J]. 山东大学耳鼻喉眼学报, 2019, 33(4): 40-42. doi:10.6040/j.issn.1673-3770.1.2019.042. SUN Xiaohan, LI Na. Application of laryngeal retention strategy in the treatment of laryngeal cancer - introduction to the clinical practice guide of the American society of clinical oncology(2017)[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(4): 40-42. doi:10.6040/j.issn.1673-3770.1.2019.042.
[5] Yang XL, Liu GL, Zang LY, et al. ZNF703 is overexpressed in papillary thyroid carcinoma tissues and mediates K1 cell proliferation[J]. Pathol Oncol Res, 2020, 26(1): 355-364. doi:10.1007/s12253-018-0494-5.
[6] Song XL, Zhu MH, Zhang FH, et al. ZFX promotes proliferation and metastasis of pancreatic cancer cells via the MAPK pathway[J]. Cell Physiol Biochem, 2018, 48(1): 274-284. doi:10.1159/000491727.
[7] Kim YJ, Jang W, Piao XM, et al. ZNF492 and GPR149 methylation patterns as prognostic markers for clear cell renal cell carcinoma: Array-based DNA methylation profiling[J]. Oncol Rep, 2019, 42(1): 453-460. doi:10.3892/or.2019.7151.
[8] Samadani AA, Nikbakhsh N, Taheri H, et al. CDX1/2 and KLF5 expression and epigenetic modulation of sonic hedgehog signaling in gastric adenocarcinoma[J]. Pathol Oncol Res, 2019, 25(3): 1215-1222. doi:10.1007/s12253-019-00594-4.
[9] Liang H, Sun H, Yang J, et al. miR-145-5p reduces proliferation and migration of hepatocellular carcinoma by targeting KLF5[J]. Mol Med Rep, 2018, 17(6): 8332-8338. doi:10.3892/mmr.2018.8880. doi:10.3892/mmr.2018.8880.
[10] Lu M, Wu Y, Zeng B, et al. CircEHMT1 inhibits metastatic potential of breast cancer cells by modulating miR-1233-3p/KLF4/MMP2 axis[J]. Biochemical and Biophysical Research Communications, 2020, 526(2): 306-313. doi:10.1016/j.bbrc.2020.03.084.
[11] Mann R. Molecular mechanisms of selector gene function and evolution[J]. Curr Opin Genet Dev, 2002, 12(5): 592-600. doi:10.1016/s0959-437x(02)00344-1.
[12] Tupler R, Perini G, Green MR. Expressing the human genome[J]. Nature, 2001, 409(6822): 832-833. doi:10.1038/35057011.
[13] Lambert SA, Jolma A, Campitelli LF, et al. The human transcription factors[J]. Cell, 2018, 172(4): 650‐665. doi:10.1016/j.cell.2018.01.029.
[14] Schmitges FW, Radovani E, Najafabadi HS, et al. Multiparameter functional diversity of human C2H2 zinc finger proteins[J]. Genome Res, 2016, 26(12): 1742-1752. doi:10.1101/gr.209643.116.
[15] Emerson RO, Thomas JH. Adaptive evolution in zinc finger transcription factors[J]. PLoS Genet, 2009, 5(1): e1000325. doi:10.1371/journal.pgen.1000325.
[16] Gamsjaeger R, Liew C, Loughlin F, et al. Sticky fingers: zinc-fingers as protein-recognition motifs[J]. Trends Biochem Sci, 2007, 32(2): 63-70. doi:10.1016/j.tibs.2006.12.007.
[17] Brown RS. Zinc finger proteins: getting a grip on RNA[J]. Curr Opin Struct Biol, 2005, 15(1): 94-98. doi:10.1016/
[18] Mackeh R, Marr AK, Fadda A, et al. C2H2-type zinc finger proteins: evolutionarily old and new partners of the nuclear hormone receptors[J]. Nucl Recept Signal, 2018, 15: 155076291880107. doi:10.1177/1550762918801071.
[19] Chen CH. The role of miR-101 and miR-135a in reprogramming of somatic cells into induced pluripotent stem cells[D]. The University of Hong Kong Libraries, Master of Philosophy, 2012. doi:10.5353/th_b4852157.
[20] Bellanger A, Donini CF, Vendrell JA, et al. The critical role of the ZNF217 oncogene in promoting breast cancer metastasis to the bone[J]. J Pathol, 2017, 242(1): 73-89. doi:10.1002/path.4882.
[21] Ma MQ, Zhang HD, Tang P, et al. Association of Kruppel-like factor 4 expression with the prognosis of esophageal squamous cell carcinoma patients[J]. Int J Clin Exp Pathol, 2014, 7(10): 6679-6685.
[22] 齐力, 侯艳, 宋丽华. 转录因子YY1促进下咽癌细胞的迁移能力[J]. 基础医学与临床, 2019, 39(9): 1320-1324. doi:10.16352/j.issn.1001-6325.2019.09.019. QI Li, HOU Yan, SONG Lihua. Transcription factor YY1 promotes the migration ability of hypopharyngeal carcinoma cells[J]. Basic & Clinical Medicine, 2019, 39(9): 1320-1324. doi:10.16352/j.issn.1001-6325.2019.09.019.
[23] Yang L, Han Y, Suarez SF, et al. A tumor suppressor and oncogene: the WT1 story[J]. Leukemia, 2007, 21(7): 1603. doi:10.1038/sj.leu.2404624.
[24] Rampal R, Figueroa ME. Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia[J]. Haematologica, 2016, 101(6): 672-679. doi:10.3324/haematol.2015.141796.
[25] Frietze S, O'Geen H, Littlepage LE, et al. Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha[J]. BMC Genom, 2014, 15(1): 520. doi:10.1186/1471-2164-15-520.
[26] Harder L, Puller AC, Horstmann MA. ZNF423: Transcriptional modulation in development and cancer[J]. Mol Cell Oncol, 2014, 1(3): e969655. doi:10.4161/23723548.2014.969655.
[27] Thomas MJ, Seto E. Unlocking the mechanisms of transcription factor YY1: are chromatin modifying enzymes the key?[J]. Gene, 1999, 236(2): 197-208. doi:10.1016/S0378-1119(99)00261-9.
[28] Park K. Characterization of functional domains within the multifunctional transcription factor, YY1[J]. J Biol Chem, 1995, 270(50): 30213-30220. doi:10.1074/jbc.270.50.30213.
[29] Shi JM, Hao AX, Zhang Q, et al. The role of YY1 in oncogenesis and its potential as a drug target in cancer therapies[J]. Curr Cancer Drug Targets, 2015, 15(2): 145-157. doi:10.2174/1568009615666150131124200.
[30] 邱广斌, 邱广蓉, 徐振明, 等. 6q25区域内一个新基因MTLC的克隆及特性分析[J]. 中华医学遗传学杂志, 2003, 20(2): 94-97. doi:10.3760/j.issn:1003-9406.2003.02.002. QIU Guangbin, QIU Guangrong, XU Zhenming, et al. Cloning and characterization of MTLC, a novel gene in 6q25[J]. Chinese Journal of Medical Genetics, 2003, 20(2): 94-97. doi:10.3760/j.issn:1003-9406.2003.02.002.
[31] Qu SY, Sun YY, Li YH, et al. YY1 directly suppresses MYCT1 leading to laryngeal tumorigenesis and progress[J]. Cancer Med, 2017, 6(6): 1389-1398. doi:10.1002/cam4.1073.
[32] Zhang ZX, Zhang WN, Sun YY, et al. CREB promotes laryngeal cancer cell migration via MYCT1/NAT10 axis[J]. Oncotargets Ther, 2018, 11: 1323-1331. doi:10.2147/ott.s156582.
[33] McConnell BB, Yang VW. Mammalian krüppel-like factors in health and diseases[J]. Physiol Rev, 2010, 90(4): 1337-1381. doi:10.1152/physrev.00058.2009.
[34] Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006, 126(4): 663-676. doi:10.1016/j.cell.2006.07.024.
[35] Ghaleb AM, Yang VW. Krüppel-like factor 4(KLF4): What we currently know[J]. Gene, 2017, 611: 27-37. doi:10.1016/j.gene.2017.02.025.
[36] 刘华松, 徐兰兰, 张军, 等. 过表达KLF4抑制非小细胞肺癌增殖及上皮间质转化的作用机制[J]. 中国现代医学杂志, 2017, 27(19): 40-44. doi:10.3969/j.issn.1005-8982.2017.19.008. LIU Huasong, XU Lanlan, ZHANG Jun, et al. Mechanisms of KLF4 over-expression in inhibiting proliferation and EMT of NSCLC[J]. China Journal of Modern Medicine, 2017, 27(19): 40-44. doi:10.3969/j.issn.1005-8982.2017.19.008.
[37] Zhao RR, Liu ZX, Xu WT, et al. Helicobacter pylori infection leads to KLF4 inactivation in gastric cancer through a TET1-mediated DNA methylation mechanism[J]. Cancer Med, 2020, 9(7): 2551-2563. doi:10.1002/cam4.2892.
[38] 李娜, 李赟, 万小亚, 等. MicroRNA-34a调控KLF4转录因子在结直肠癌5-Fu耐药中的作用[J]. 中国肿瘤, 2020, 29(2): 148-153. doi:10.11735/j.issn.1004-0242.2020.02.A011. LI Na, LI Yun, WAN Xiaoya, et al. KLF4 transcription factor regulated by MicroRNA-34a in 5-fu chemotherapy resistance of colorectal cancer[J]. China Cancer, 2020, 29(2): 148-153. doi:10.11735/j.issn.1004-0242.2020.02.A011.
[39] 潘恩山, 李煜罡, 朱晓光. miR-375通过抑制KLF4促进前列腺癌细胞的迁移和侵袭[J]. 重庆医学, 2017, 46(23): 3184-3188. doi:10.3969/j.issn.1671-8348.2017.23.005. PAN Enshan, LI Yugang, ZHU Xiaoguang. miR-375 promotes prostate cancer cell migration and invasion by targeting KLF4[J]. Chongqing Medicine, 2017, 46(23): 3184-3188. doi:10.3969/j.issn.1671-8348.2017.23.005.
[40] Guo Y, An R, Zhao R, et al. miR-375 exhibits a more effective tumor-suppressor function in laryngeal squamous carcinoma cells by regulating KLF4 expression compared with simple co-transfection of miR-375 and miR-206[J]. Oncol Rep, 2016, 36(2): 952-960. doi:10.3892/or.2016.4852.
[41] Zheng TL, Cen K. MiR-92a inhibits proliferation and promotes apoptosis of OSCC cells through Wnt/β-catenin signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2020, 24(9): 4803-4809. doi:10.26355/eurrev_202005_21169.
[42] Greco A, de Virgilio A, Rizzo MI, et al. The prognostic role of E-cadherin and β-catenin overexpression in laryngeal squamous cell carcinoma[J]. Laryngoscope, 2016, 126(4): E148-E155. doi:10.1002/lary.25736.
[43] Chanchevalap S. Kruppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells[J]. Nucleic Acids Res, 2006, 34(4): 1216-1223. doi:10.1093/nar/gkl014.
[44] Kadonaga JT, Carner KR, Masiarz FR, et al. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain[J]. Cell, 1987, 51(6): 1079-1090. doi:10.1016/0092-8674(87)90594-0.
[45] Li XC, Liu XS, Xu YJ, et al. KLF5 promotes hypoxia-induced survival and inhibits apoptosis in non-small cell lung cancer cells via HIF-1α[J]. Int J Oncol, 2014, 45(4): 1507-1514. doi:10.3892/ijo.2014.2544.
[46] Yang Y, Nakagawa H, Tetreault MP, et al. Loss of transcription factor KLF5 in the context of p53 ablation drives invasive progression of human squamous cell cancer[J]. Cancer Res, 2011, 71(20): 6475-6484. doi:10.1158/0008-5472.can-11-1702.
[47] Yang YZ, Tarapore RS, Jarmel MH, et al. p53 mutation alters the effect of the esophageal tumor suppressor KLF5 on keratinocyte proliferation[J]. Cell Cycle, 2012, 11(21): 4033-4039. doi:10.4161/cc.22265.
[48] Liu FF, Dong L, Yang X, et al. KLF5 silence attenuates proliferation and epithelial-mesenchymal transition induction in Hep-2 cells through NF-κB signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23(9): 3867-3875. doi:10.26355/eurrev_201905_17814.
[49] Zhang L, Sun J, Wang B, et al. MicroRNA-10b triggers the epithelial-mesenchymal transition(EMT)of laryngeal carcinoma hep-2 cells by directly targeting the E-cadherin[J]. Appl Biochem Biotechnol, 2015, 176(1): 33-44. doi:10.1007/s12010-015-1505-6.
[50] Wu X, Ruan YY, Jiang H, et al. MicroRNA-424 inhibits cell migration, invasion, and epithelial mesenchymal transition by downregulating doublecortin-like kinase 1 in ovarian clear cell carcinoma[J]. Int J Biochem Cell Biol, 2017, 85: 66-74. doi:10.1016/j.biocel.2017.01.020.
[51] Mao XH, Miao SS, He HJ, et al. Krüppel-like factor 5: a novel biomarker for lymph node metastasis and recurrence in supraglottic squamous cell laryngeal carcinoma[J]. Tumor Biol, 2014, 35(1): 623-629. doi:10.1007/s13277-013-1086-3.
[52] Liu JY, Lu JB, Xu Y. MicroRNA-153 inhibits the proliferation and invasion of human laryngeal squamous cell carcinoma by targeting KLF5[J]. Exp Ther Med, 2016, 11(6): 2503-2508. doi:10.3892/etm.2016.3189.
[53] Galan-Caridad JM, Harel S, Arenzana TL, et al. Zfx controls the self-renewal of embryonic and hematopoietic stem cells[J]. Cell, 2007, 129(2): 345-357. doi:10.1016/j.cell.2007.03.014.
[54] Arnold A, Soong CP. New role for ZFX in oncogenesis[J]. Cell Cycle, 2014, 13(22): 3465-3466. doi:10.4161/15384101.2014.980693.
[55] Yang F, Ma H, Feng L, et al. Zinc finger protein x-linked(ZFX)contributes to patient prognosis, cell proliferation and apoptosis in human laryngeal squamous cell carcinoma[J]. Int J Clin Exp Pathol, 2015, 8(11): 13886-13899.
[56] Zhang YM, Hu HL. Long non-coding RNA CCAT1/miR-218/ZFX axis modulates the progression of laryngeal squamous cell cancer[J]. Tumour Biol, 2017, 39(6): 101042831769941. doi:10.1177/1010428317699417.
[1] WANG MeiOverview,LI ZhihaiGuidance. Laryngeal cancer stem cells: potential therapeutic targets for overcoming multidrug resistance [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(4): 120-128.
[2] WANG Xiaoting, CHEN Zhengnong, YI Hongliang. Transcriptomic analysis of glutamine deprivation on laryngeal carcinoma cells [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(2): 26-31.
[3] LI Yanjie, JIA Jian, YANG Ping, WAN Baoluo. Study on the value of tumor abnormal protein in clinical diagnosis of laryngeal carcinoma [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(5): 70-74.
[4] To investigate the swallowing function recovery on 23 cases of supraglottic laryngeal carcinoma postoperation. MethodsFrom 2016 to 2019, a retrospective swallowing function analysis was performed on 23 cases of supraglottic laryngeal carcinoma. All of the patients underwent horizontal hemilaryngectomy and reconstruction with tongue flap. The M.D. Anderson Dysphasia Inventory(MDADI)was used to evaluate the swallowing function from emotional dimension, social function dimension, and physiological dimension before and after operation. Results2 patients died during follow-up period.1 case lost follow-up. 20 patients recovered to normal diet. The overall swallowing median score was 90.00[80.00,100.00], and the postoperative score median was 80.00[80.00,80.00](P=0.359).The median score of emotion dimension was 91.67[77.50,93.33], 80.00[80.00,83.33](P=0.065)after operation. The median score of social function was 90.00[80.00,96.00]before surgery, and 84.00[80.00,92.00](P=0.587)after surgery. Physiological function median score was 83.75[76.25,89.38], 80.00[75.00,84.38](P=0.018)after surgery. ConclusionTongue flap can improve the swallowing function and the quality of patient life after the horizontal hemilaryngectomy.. The swallowing function recovery study on tongue flap after horizontal hemilaryngectomy [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2020, 34(5): 127-131.
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[6] LI Xiaoming, SONG Qi, LI Hongxia, TAO Zhenfeng, SHEN Yupeng, XIAO Shufen. Reconstruction of hypopharyngeal defects after ablation of advanced head and neck squamous carcinoma involving hypophaynx with pectoralis major myocutaneous flap. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(3): 4-9.
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[8] LIN Dan, DONG Wei-da, LU Mei-ping, XING Guang-qian, DONG Jia-di, ZHANG Wei-qiang. The association between rs2910164 G>C polymorphism in pre-microRNA-146a and laryngeal cancer in Jiangsu Han population [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2014, 28(2): 46-50.
[10] SHI Da-zhi1, LUO Zhi-qiang1, ZHOU Jun2. Expression and significance of serum soluble tumor necrosis factor  receptor  Ⅰ and  Ⅱ in patients with laryngeal cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2010, 24(5): 10-12.
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