国际口腔医学杂志

国际口腔医学杂志 ›› 2023, Vol. 50 ›› Issue (3): 314-320.doi: 10.7518/gjkq.2023043

• 综述 • 上一篇    下一篇

性别决定基因盒9在口腔鳞状细胞癌作用机制和治疗中的研究进展

盛南宁1,2(),王珏1,3(),南欣荣1,4   

  1. 1.山西医科大学口腔医学院 太原 030001
    2.口腔疾病防治与新材料山西省重点实验室 太原 030001
    3.山西医科大学第一医院口腔修复科 太原 030001
    4.山西医科大学第一医院口腔颌面外科 太原 030001
  • 收稿日期:2022-09-15 修回日期:2023-02-27 出版日期:2023-05-01 发布日期:2023-05-16
  • 通讯作者: 王珏
  • 作者简介:盛南宁，医师，硕士，Email：sheng_415@163.com
  • 基金资助:
    国家自然科学基金(82003146)

Research progress on mechanism and treatment of sex-determining region Y box 9 in oral squamous cell carcinoma

Sheng Nanning1,2(),Wang Jue1,3(),Nan Xinrong1,4   

  1. 1.School of Stomatology, Shanxi Medical University, Taiyuan 030001, China
    2.Shanxi Province Key Laboratory of Oral Disease Prevention and New Materials, Taiyuan 030001, China
    3.Dept. of Prosthodontics, First Hospital of Shanxi Medical University, Taiyuan 030001, China
    4.Dept. of Oral and Maxillofacial Surgery, First Hospital of Shanxi Medical University, Taiyuan 030001, China
  • Received:2022-09-15 Revised:2023-02-27 Online:2023-05-01 Published:2023-05-16
  • Contact: Jue Wang
  • Supported by:
    National Natural Science Foundation of China(82003146)

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摘要：

口腔鳞状细胞癌（OSCC）是头颈部常见的恶性肿瘤，预后较差，生存率长期未见提高。性别决定基因盒9（SOX9）在全身各个系统的恶性肿瘤均有表达，已成为肿瘤表面标志物及靶向治疗方面的研究热点。在OSCC中，SOX9的作用复杂多样，可能通过诱导化疗耐药等干细胞特征的产生导致不良预后。了解其在OSCC发生发展及治疗预后中的具体作用及机制有助于早日攻克OSCC预后生存难题。本文就SOX9在OSCC的早期诊断和预防、发生发展中的作用和机制以及对治疗预后的影响等方面进行综述。

关键词: 性别决定基因盒9, 口腔鳞状细胞癌, 肿瘤表面标志物

Abstract:

Oral squamous cell carcinoma is the most common malignancy of the head and neck. It has poor prognosis and survival rate that has not improved for many years. Sex-determining region Y box 9 (SOX9) is expressed in malignant tumors of various systems throughout the body. In recent years, SOX9 has become a hotspot in research on tumor surface markers and tumor-targeted therapy. In oral squamous cell carcinoma, SOX9 exhibits complex and diverse effects and may lead to poor prognosis by inducing the development of stem cell features, such as chemotherapy resistance. Understanding the specific role and mechanism of SOX9 in the occurrence, development, and prognosis of OSCC is important to improve the prognosis and survival of oral squamous cell carcinoma. In this paper, the role and mechanism of SOX9 in the early diagnosis, prevention, occurrence, development, and treatment prognosis of oral squamous cell carcinoma are discussed.

Key words: sex-determining region Y box 9, oral squamous cell carcinoma, tumor surface marker

中图分类号: 

  • R 739.8
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 Ng JH, Iyer NG, Tan MH, et al. Changing epide-miology of oral squamous cell carcinoma of the ton-gue: a global study[J]. Head Neck, 2017, 39(2): 297-304.
3 Ong YLR, Tivey D, Huang L, et al. Factors affec-ting surgical mortality of oral squamous cell carcinoma resection[J]. Int J Oral Maxillofac Surg, 2021, 50(1): 1-6.
4 Luiz ST, Modolo F, Mozzer I, et al. Immunoexpression of SOX-2 in oral leukoplakia[J]. Oral Dis, 2018, 24(8): 1449-1457.
5 de Vicente JC, Donate-Pérez Del Molino P, Rodrigo JP, et al. SOX2 expression is an independent predictor of oral cancer progression[J]. J Clin Med, 2019, 8(10): 1744.
6 陈志鹏, 李欢, 陈树伟, 等. 干细胞转录因子SOX8在口腔鳞状细胞癌中的表达及意义[J]. 实用医学杂志, 2019, 35(24): 3765-3768.
Chen ZP, Li H, Chen SW, et al. Expression and significance of stem cell transcription factor SOX8 in oral squamous cell carcinoma[J]. J Pract Med, 2019, 35(24): 3765-3768.
7 Jo A, Denduluri S, Zhang BS, et al. The versatile functions of Sox9 in development, stem cells, and human diseases[J]. Genes Dis, 2014, 1(2): 149-161.
8 Li LX, Fu QW, Shao JH, et al. Oct4 facilitates chondrogenic differentiation of mesenchymal stem cells by mediating CIP2A expression[J]. Cell Tissue Res, 2022, 389(1): 11-21.
9 Sreenivasan R, Gonen N, Sinclair A. SOX genes and their role in disorders of sex development[J]. Sex Dev, 2022, 16(2/3): 80-91.
10 韩文慧, 邓慧兰, 王辉, 等. PRAME mRNA和SOX9 mRNA在肺腺癌中的表达及临床意义[J]. 国际检验医学杂志, 2021, 42(9): 1069-1073.
Han WH, Deng HL, Wang H, et al. Expression of PRAME mRNA and SOX9 mRNA in lung adenocarcinoma and its clinical significance[J]. Int J Lab Med, 2021, 42(9): 1069-1073.
11 Song SM, Wang ZN, Li Y, et al. PPARδ interacts with the hippo coactivator YAP1 to promote SOX9 expression and gastric cancer progression[J]. Mol Cancer Res, 2020, 18(3): 390-402.
12 Nouri M, Massah S, Caradec J, et al. Transient Sox9 expression facilitates resistance to androgen-targe-ted therapy in prostate cancer[J]. Clin Cancer Res, 2020, 26(7): 1678-1689.
13 Domenici G, Aurrekoetxea-Rodríguez I, Simões BM, et al. A Sox2-Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells[J]. Oncogene, 2019, 38(17): 3151-3169.
14 Yuan XD, Li J, Coulouarn C, et al. SOX9 expression decreases survival of patients with intrahepatic cholangiocarcinoma by conferring chemoresistance[J]. Br J Cancer, 2018, 119(11): 1358-1366.
15 Ruan HH, Hu SY, Zhang HY, et al. Upregulated SOX9 expression indicates worse prognosis in solid tumors: a systematic review and meta-analysis[J]. Oncotarget, 2017, 8(68): 113163-113173.
16 Misuno K, Liu XJ, Feng SZ, et al. Quantitative proteomic analysis of sphere-forming stem-like oral cancer cells[J]. Stem Cell Res Ther, 2013, 4(6): 15.
17 刘艳玲, 赵曦, 余丽, 等. SOX-9在口腔鳞状细胞癌组织中的表达及其临床意义[J].口腔医学研究, 2019, 35(5): 439-442.
Liu YL, Zhao X, Yu L, et al. Expression and clinical significance of SOX-9 in human oral squamous cell carcinoma[J]. J Oral Sci Res, 2019, 35(5): 439-442.
18 代冬, 冯小东. MUC15、SOX9及EGFR在口腔鳞癌中的表达及意义[J]. 临床口腔医学杂志, 2020, 36(7): 391-394.
Dai D, Feng XD. Expression and correlation of MUC15, SOX9 and EGFR in oral squamous cell carcinoma[J]. J Clin Stomatol, 2020, 36(7): 391-394.
19 Li YC, Chang JT, Chiu C, et al. Areca nut contri-butes to oral malignancy through facilitating the conversion of cancer stem cells[J]. Mol Carcinog, 2016, 55(5): 1012-1023.
20 Yu CC, Chang YC. Enhancement of cancer stem-like and epithelial-mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: reversal by targeting SNAIL[J]. Toxicol Appl Pharmacol, 2013, 266(3): 459-469.
21 Yu CC, Tsai LL, Wang ML, et al. miR145 targets the SOX9/ADAM17 axis to inhibit tumor-initiating cells and IL-6-mediated paracrine effects in head and neck cancer[J]. Cancer Res, 2013, 73(11): 3425-3440.
22 邹忠涛, 胡温庭, 曹巍, 等. 性别决定基因盒9的表达水平与口腔鳞状细胞癌转移相关性的研究[J]. 中华口腔医学杂志, 2018, 53(10): 688-693.
Zou ZT, Hu WT, Cao W, et al. Relationship between expressionlevel of sex-determining region Y box 9 and metastasis of oral squamous cell carcinoma[J]. Chin J Stomatol, 2018, 53(10): 688-693.
23 Sumita Y, Yamazaki M, Maruyama S, et al. Cytoplasmic expression of SOX9 as a poor prognostic factor for oral squamous cell carcinoma[J]. Oncol Rep, 2018, 40(5): 2487-2496.
24 Sosa MS, Parikh F, Maia AG, et al. NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes[J]. Nat Commun, 2015, 6: 6170.
25 Haga K, Yamazaki M, Maruyama S, et al. Crosstalk between oral squamous cell carcinoma cells and cancer-associated fibroblasts via the TGF-β/SOX9 axis in cancer progression[J]. Transl Oncol, 2021, 14(12): 101236.
26 Valenta T, Hausmann G, Basler K. The many faces and functions of β-catenin[J]. Embo J, 2012, 31(12): 2714-2736.
27 Zhang HY, Cai K, Wang J, et al. MiR-7, inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and reverses the EMT of breast cancer stem cells by downregulating the STAT3 pathway[J]. Stem Cells, 2014, 32(11): 2858-2868.
28 冯蓓, 王媛, 刘宁宁. HPV-16E6/E7通过调控上皮间质转化对宫颈癌模型小鼠存活、肿瘤生长及转移的影响[J]. 医学分子生物学杂志, 2019, 16(1): 46-51.
Feng B, Wang Y, Liu NN. Effects of HPV-16E6/E1 on survival, tumor growth and metastasis of cervical cancer model mice by regulating epithelial mesenchymal transformation[J]. J Med Mol Biol, 2019, 16(1): 46-51.
29 Hirano T, Saito D, Yamada H, et al. TGF‑β1 induces N‑cadherin expression by upregulating Sox9 expression and promoting its nuclear translocation in human oral squamous cell carcinoma cells[J]. Oncol Lett, 2020, 20(1): 474-482.
30 黄盛, 张七援, 何爱娥, 等. 性别决定区Y框蛋白9诱导人口腔鳞状细胞癌CAL27微管形成和上皮间质转化的机制初探[J]. 华西口腔医学杂志, 2021, 39(1): 74-80.
Huang S, Zhang QY, He AE, et al. Sex determining region Y-box 9 induced microtubule formation and epithelial mesenchymal transition in human oral squamous cell carcinoma CAL27 cells[J]. West China J Stomatol, 2021, 39(1): 74-80.
31 杨文丽, 孙明磊, 张朋, 等. 下调性别决定区Y框蛋白9对口腔鳞癌细胞上皮间质转化及克隆能力的影响[J]. 华西口腔医学杂志, 2019, 37(1): 13-18.
Yang WL, Sun ML, Zhang P, et al. Effect of down-regulation of sex determining region Y-box 9 on epithelial mesenchymal transition and cloning of oral squamous carcinoma cells[J]. West China J Stomatol, 2019, 37(1): 13-18.
32 Lyu Q, Jin L, Yang XB, et al. LncRNA MINCR activates Wnt/β-catenin signals to promote cell prolife-ration and migration in oral squamous cell carcinoma[J]. Pathol Res Pract, 2019, 215(5): 924-930.
33 Iwai S, Yonekawa A, Harada C, et al. Involvement of the Wnt‑β‑catenin pathway in invasion and migration of oral squamous carcinoma cells[J]. Int J Oncol, 2010, 37(5): 1095-1103.
34 Vetro A, Ciccone R, Giorda R, et al. XX males SRY negative: a confirmed cause of infertility[J]. J Med Genet, 2011, 48(10): 710-712.
35 Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma[J]. Proc Natl Acad Sci U S A, 2007, 104(3): 973-978.
36 Szafarowski T, Szczepanski MJ. Cancer stem cells in head and neck squamous cell carcinoma[J]. Otolaryngol Pol, 2014, 68(3): 105-111.
37 Li XR, Zhong YL, Lu J, et al. Correction: mtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features[J]. Oncotarget, 2017, 8(4): 7208-7213.
38 Wang P, Wan WW, Xiong SL, et al. Cancer stem-like cells can be induced through dedifferentiation under hypoxic conditions in glioma, hepatoma and lung cancer[J]. Cell Death Discov, 2017, 3: 16105.
39 Oshimori N, Oristian D, Fuchs E. TGF‑β promotes heterogeneity and drug resistance in squamous cell carcinoma[J]. Cell, 2015, 160(5): 963-976.
40 Qu Y, He Y, Yang Y, et al. ALDH3A1 acts as a prognostic biomarker and inhibits the epithelial mesenchymal transition of oral squamous cell carcinoma through IL-6/STAT3 signaling pathway[J]. J Cancer, 2020, 11(9): 2621-2631.
41 MoonY, KimD, SohnH, et al. Effect of CD133 overexpression on the epithelial-to-mesenchymal transition in oral cancer cell lines[J]. Clin Exp Metastasis, 2016, 33(5): 487-496.
42 Huang CF, Xu XR, Wu TF, et al. Correlation of ALDH1, CD44, OCT4 and SOX2 in tongue squamous cell carcinoma and their association with disease progression and prognosis[J]. J Oral Pathol Med, 2014, 43(7): 492-498.
43 Lee SH, Oh SY, Do SI, et al. SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma[J]. Br J Cancer, 2014, 111(11): 2122-2130.
44 Chen DM, Wu MS, Li Y, et al. Targeting BMI1+ cancer stem cells overcomes chemoresistance and inhi-bits metastases in squamous cell carcinoma[J]. Cell Stem Cell, 2017, 20(5): 621-634.e6.
45 Le PN, Keysar SB, Miller B, et al. Wnt signaling dynamics in head and neck squamous cell cancer tumor-stroma interactions[J]. Mol Carcinog, 2019, 58(3): 398-410.
46 Argiris A, Harrington KJ, Tahara M, et al. Evidence-based treatment options in recurrent and/or metasta-tic squamous cell carcinoma of the head and neck[J]. Front Oncol, 2017, 7: 72.
47 Zhao ZL, Zhang L, Huang CF, et al. NOTCH1 inhibition enhances the efficacy of conventional chemotherapeutic agents by targeting head neck cancer stem cell[J]. Sci Rep, 2016, 6: 24704.
48 Oh M, Son C, Rho SB, et al. Stem cell factor SOX9 interacts with a cell death regulator RIPK1 and results in escape of cancer stem cell death[J]. Cells, 2022, 11(3): 363.
49 Higashihara T, Yoshitomi H, Nakata Y, et al. Sex determining region Y box 9 induces chemoresistance in pancreatic cancer cells by induction of putative cancer stem cell characteristics and its high expression predicts poor prognosis[J]. Pancreas, 2017, 46(10): 1296-1304.
50 Sun JH, Chen Q, Ma JL. Notch-Sox9 axis mediates hepatocyte dedifferentiation in KrasG12V-induced zebrafish hepatocellular carcinoma[J]. Int J Mol Sci, 2022, 23(9): 4705.
51 Hasegawa T, Yanamoto S, Otsuru M, et al. Retrospective study of treatment outcomes after postope-rative chemoradiotherapy in Japanese oral squamous cell carcinoma patients with risk factors of recurrence[J]. Oral Surg Oral Med Oral Pathol Oral Ra-diol, 2017, 123(5): 524-530.
52 Liu XG, Zhao TD, Yuan Z, et al. MIR600HG spon-ges miR-125a-5p to regulate glycometabolism and cisplatin resistance of oral squamous cell carcinoma cells via mediating RNF44 [J]. Cell Death Discov, 2022, 8(1): 216.
53 Li T, Cheng DM, Guo J, et al. SOX9 and IL1A as the potential gene biomarkers of the oral cancer[J]. Comb Chem High Throughput Screen, 2022. doi:10.2174/1386207325666220628091041 .
doi: 10.2174/1386207325666220628091041
54 Ullah MA, Islam NN, Sarkar B, et al. Bioinforma-tics analysis on the prognostic significance of SOX9 gene and its transcriptional product in colorectal cancer[J]. Hum Gene, 2022, 33: 201043.
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[2] 王昆润. 长期单侧鼻呼吸对头颅发育有不利影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[3] 彭国光. 颈淋巴清扫术中颈交感神经干的解剖变异[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 杨凯. 淋巴化疗的药物运载系统及其应用现状[J]. 国际口腔医学杂志, 1999, 26(05): .
[5] 康非吾. 种植义齿下部结构生物力学研究进展[J]. 国际口腔医学杂志, 1999, 26(05): .
[6] 柴枫. 可摘局部义齿用Co-Cr合金的激光焊接[J]. 国际口腔医学杂志, 1999, 26(04): .
[7] 孟姝,吴亚菲,杨禾. 伴放线放线杆菌产生的细胞致死膨胀毒素及其与牙周病的关系[J]. 国际口腔医学杂志, 2005, 32(06): 458 -460 .
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