国际口腔医学杂志

国际口腔医学杂志 ›› 2025, Vol. 52 ›› Issue (3): 358-365.doi: 10.7518/gjkq.2025045

• 论著 • 上一篇    

支链氨基酸转氨酶1在口腔鳞状细胞癌中的表达及其功能研究

李熠洁1(),原振英1,李明2()   

  1. 1.长沙市口腔医院牙体美容科 长沙 410000
    2.中南大学湘雅口腔医（学）院 口腔健康研究湖南省重点实验室 长沙 410000
  • 收稿日期:2024-04-25 修回日期:2024-10-29 出版日期:2025-05-01 发布日期:2025-04-30
  • 通讯作者: 李明
  • 作者简介:李熠洁，医师，硕士，Email：327623445@qq.com
  • 基金资助:
    湖南省重点研发项目(2022SK2052)

Expression and function of branch-chain amino acid transaminase 1 in oral squamous cell carcinoma

Yijie Li1(),Zhenying Yuan1,Ming Li2()   

  1. 1.Dept. of Dental Aesthetics, Changsha Stomatological Hospital, Changsha 410000, China
    2.Xiangya School/Hospital of Stomatology, Central South University, Key Laboratory of Oral Health Research in Hunan Province, Changsha 410000, China
  • Received:2024-04-25 Revised:2024-10-29 Online:2025-05-01 Published:2025-04-30
  • Contact: Ming Li
  • Supported by:
    Key Research and Development Project of Hunan Province(2022SK2052)

RichHTML

0

PDF (PC)

3

摘要：

目的 分析支链氨基酸转氨酶1（BCAT1）在口腔鳞状细胞癌（OSCC）中的表达及生物功能。 方法 采用生物信息学分析BCAT1在头颈部鳞状细胞癌（HNSC）患者中的表达、与患者预后的关系。随后，选取2021—2022年在中南大学湘雅口腔医院口腔颌面外科确诊的40名OSCC患者，检测癌及癌旁组织中BCAT1基因表达。分析人OSCC细胞系和正常口腔角质细胞中BCAT1基因表达。质粒过表达或敲低BCAT1基因后，采用细胞增殖、划痕和侵袭实验分别检测人OSCC细胞增殖、迁移和侵袭能力改变。 结果 BCAT1在the Cancer Genome Atlas（TCGA）数据库中HNSC患者癌组织中高表达，且是患者的独立预后因素之一和潜在诊断标志物。细胞实验结果表明BCAT1在人OSCC组织和细胞系中表达上调，并调控OSCC细胞增殖、迁移和侵袭。 结论 BCAT1基因是人OSCC的潜在治疗靶点。

关键词: 支链氨基酸转氨酶1, 口腔鳞状细胞癌, 头颈鳞状细胞癌, 增殖, 迁移, 侵袭

Abstract:

Objective This study aimed to analyze the expression and biological function of branch-chain amino acid transaminase 1 (BCAT1) in oral squamous cell carcinoma (OSCC). Methods The expression of BCAT1 in head and neck squamous cell carcinoma (HNSC) patients and its relationship with prognosis were analyzed by bioinformatics. To detect BCAT1 gene expression in tumor and adjacent tissues, we selected patients with OSCC diagnosed in the Department of Oral and Maxillofacial Surgery, Xiangya Stomatology Hospital, Central South University from 2021 to 2022. BCAT1 gene expression in human OSCC cell line and normal oral keratinocytes was analyzed. After plasmid overexpression or knockdown of BCAT1 gene, the proliferation, migration, and invasion ability of human OSCC cells were detected by cell proliferation, wound-healing, and invasion assays, respectively. Results BCAT1 was highly expressed in cancer tissues of HNSC patients in the Cancer Genome Atlas (TCGA) database and was one of the independent prognostic factors and potential diagnostic markers of patients. Results of cellular assays showed that BCAT1 expression was upregula-ted in human OSCC tissues or cell lines, thereby regulating the proliferation, migration, and invasion of OSCC cells. Conclusion BCAT1 gene is a potential therapeutic target for human OSCC.

Key words: branch-chain amino acid transaminase 1, oral squamous cell carcinoma, head and neck squamous cell carcinoma, proliferation, migration, invasion

中图分类号: 

  • R739.8

图 1

BCAT1基因在HNSC中高表达，且与患者较差生存预后有关A：BCAT1表达、临床分级和病理分期与HNSC患者生存预后有关；B：BCAT1表达是HNSC患者生存的独立预后因素；C：BCAT1基因在HNSC癌组织中较正常组织表达上调；D：BCAT1表达高的HNSC患者生存预后差；E：ROC曲线显示BCAT1预测HNSC患病的AUC为0.773（95%CI：0.707~0.839）。"

图 2

BCAT1基因和蛋白在OSCC组织中表达上调A：BCAT1基因在OSCC组织中高表达；B：BCAT1蛋白在正常组织中几乎无表达（显微镜 ×100）；C：BCAT1蛋白在OSCC组织中表达上调（显微镜 ×100）；D：BCAT1蛋白在OSCC组织中高表达。"

图 3

BCAT1基因和蛋白在OSCC细胞系中高表达A：BCAT1基因在OSCC细胞系中表达上调；B：BCAT1蛋白在OSCC细胞中表达上调。***：P<0.001。"

图 4

敲低BCAT1基因对SCC9细胞增殖、迁移和侵袭能力的影响A：qPCR检测BCAT1在SCC9细胞中的敲低效果；B：Western blot检测BCAT1蛋白在SCC9细胞中的敲低效果；C：CCK-8检测BCAT1敲低后SCC9细胞增殖能力改变；D：划痕实验检测BCAT1敲低后SCC9细胞迁移能力改变（× 100）；E：Transwell实验检测BCAT1敲低后SCC9细胞侵袭能力改变（× 100）。*：P<0.05，***：P<0.001。"

图 5

BCAT1过表达对CAL27细胞增殖、迁移和侵袭能力的影响A：RT-PCR检测BCAT1在CAL27细胞中的过表达效果；B：Western blot检测BCAT1蛋白在CAL27细胞中的过表达效果；C：CCK-8检测BCAT1过表达后CAL27细胞增殖能力改变；D：划痕实验检测BCAT1过表达对CAL27细胞迁移能力的影响（× 100）；E：Transwell实验检测BCAT1过表达对CAL27细胞侵袭能力的影响（× 100）。*：P<0.05；***：P<0.001。"

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 Shah JP, Gil Z. Current concepts in management of oral cancer: surgery[J]. Oral Oncol, 2009, 45(4/5): 394-401.
3 Rennemo E, Zätterström U, Boysen M. Outcome of local failures after oral cancer-recurrence vs. se-cond primary[J]. J Oral Pathol Med, 2010, 39(9): 657-661.
4 Ananieva EA, Wilkinson AC. Branched-chain amino acid metabolism in cancer[J]. Curr Opin Clin Nutr Metab Care, 2018, 21(1): 64-70.
5 Oktyabri D, Ishimura A, Tange S, et al. DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines[J]. Biochimie, 2016, 123: 20-31.
6 Xu M, Liu QQ, Jia YL, et al. BCAT1 promotes tumor cell migration and invasion in hepatocellular carcinoma[J]. Oncol Lett, 2016, 12(4): 2648-2656.
7 Shu X, Zhan PP, Sun LX, et al. BCAT1 activates PI3K/AKT/mTOR pathway and contributes to the angiogenesis and tumorigenicity of gastric cancer[J]. Front Cell Dev Biol, 2021, 9: 659260.
8 Zhang L, Han JQ. Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function[J]. Biochem Biophys Res Commun, 2017, 486(2): 224-231.
9 Xu Y, Yu WM, Yang TT, et al. Overexpression of BCAT1 is a prognostic marker in gastric cancer[J]. Hum Pathol, 2018, 75: 41-46.
10 Zeng B, Zhang X, Zhao JL, et al. The role of DNMT1/hsa-miR-124-3p/BCAT1 pathway in regulating growth and invasion of esophageal squamous cell carcinoma[J]. BMC Cancer, 2019, 19(1): 609.
11 Lin XM, Tan ST, Fu L, et al. BCAT1 overexpression promotes proliferation, invasion, and Wnt signaling in non-small cell lung cancers[J]. Onco Targets Ther, 2020, 13: 3583-3594.
12 Zhu ZW, Achreja A, Meurs N, et al. Tumour-reprogrammed stromal BCAT1 fuels branched-chain ketoacid dependency in stromal-rich PDAC tumours[J]. Nat Metab, 2020, 2(8): 775-792.
13 Zhu WJ, Shao YQ, Peng Y. MicroRNA-218 inhibits tumor growth and increases chemosensitivity to CDDP treatment by targeting BCAT1 in prostate cancer[J]. Mol Carcinog, 2017, 56(6): 1570-1577.
14 乌守恒, 曾晓峰, 王萍, 等. 宫颈癌组织中c-myc、bcat1的表达及其临床意义[J]. 四川大学学报(医学版), 2018, 49(5): 725-730.
Wu SH, Zeng XF, Wang P, et al. The expression and significance of c-myc and bcat1 in cervical cancer[J]. J Sichuan Univ (Med Sci Ed), 2018, 49(5): 725-730.
15 Tönjes M, Barbus S, Park YJ, et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1[J]. Nat Med, 2013, 19(7): 901-908.
16 Zheng YH, Hu WJ, Chen BC, et al. BCAT1, a key prognostic predictor of hepatocellular carcinoma, promotes cell proliferation and induces chemoresistance to cisplatin[J]. Liver Int, 2016, 36(12): 1836-1847.
17 Qi LN, Xiang BD, Wu FX, et al. Circulating tumor cells undergoing EMT provide a metric for diagnosis and prognosis of patients with hepatocellular carcinoma[J]. Cancer Res, 2018, 78(16): 4731-4744.
18 Amorim Franco TM, Favrot L, Vergnolle O, et al. Mechanism-based inhibition of the mycobacterium tuberculosis branched-chain aminotransferase by d- and l-cycloserine[J]. ACS Chem Biol, 2017, 12(5): 1235-1244.
19 Sweatt AJ, Garcia-Espinosa MA, Wallin R, et al. Branched-chain amino acids and neurotransmitter me-tabolism: expression of cytosolic branched-chain am-inotransferase (BCATc) in the cerebellum and hippocampus[J]. J Comp Neurol, 2004, 477(4): 360-370.
20 Yu MD, Zhao QW, Li JX, et al. BCAT1 promotes lung adenocarcinoma progression through enhanced mitochondrial function and NF‑κB pathway activation[J]. J Zhejiang Univ Sci B, 2022, 23(9): 760-769.
21 Wegermann K, Henao R, Diehl AM, et al. Branched chain amino acid transaminase 1 (BCAT1) is overexpressed and hypomethylated in patients with non-alcoholic fatty liver disease who experience adverse clinical events: a pilot study[J]. PLoS One, 2018, 13(9): e0204308.
22 Liu R, Liu J, Wu P, et al. Flotillin-2 promotes cell proliferation via activating the c-Myc/BCAT1 axis by suppressing miR-33b-5p in nasopharyngeal carcinoma[J]. Aging, 2021, 13(6): 8078-8094.
23 Wang HM, Wang F, Ouyang WY, et al. BCAT1 overexpression regulates proliferation and c-Myc/GLUT1 signaling in head and neck squamous cell carcinoma[J]. Oncol Rep, 2021, 45(5): 52.
24 Zhou W, Feng XL, Ren CP, et al. Over-expression of BCAT1, a c-Myc target gene, induces cell proli-feration, migration and invasion in nasopharyngeal carcinoma[J]. Mol Cancer, 2013, 12: 53.
25 Ding YF, Wang XQ, Lu SW, et al. BCAT1, as a prognostic factor for HCC, can promote the development of liver cancer through activation of the AKT signaling pathway and EMT[J]. J Mol Histol, 2023, 54(1): 25-39.
[1] 卢妍蓓,李正娟,雷蕾,罗晶晶. 磷脂酰肌醇3激酶相关放射抵抗机制在口腔鳞状细胞癌中的研究进展[J]. 国际口腔医学杂志, 2025, 52(2): 246-256.
[2] 李京哲, 张素欣. 磷脂酰肌醇3-激酶/蛋白激酶B通路抑制剂在口腔鳞状细胞癌中的研究进展[J]. 国际口腔医学杂志, 2025, 52(1): 34-41.
[3] 李冰芷, 刘云坤, 王文轩, 侯泽宇, 唐金茹, 李龙江. 口腔鳞状细胞癌嗜神经侵袭的研究进展[J]. 国际口腔医学杂志, 2024, 51(3): 362-367.
[4] 王文轩,刘云坤,李冰芷,黄能文,侯泽宇,唐金茹,李龙江. 晚期糖基化终产物在口腔鳞状细胞癌发展及治疗的研究进展[J]. 国际口腔医学杂志, 2024, 51(2): 208-216.
[5] 周金阔,张晋弘,史晓晶,刘广顺,姜磊,刘倩峰. 长链非编码RNA小核仁RNA宿主基因22调控微小RNA-27b-3p对口腔鳞状细胞癌细胞增殖、侵袭和迁移的影响[J]. 国际口腔医学杂志, 2024, 51(1): 52-59.
[6] 李立恒,王蕊,王晓明,张智轶,张璇,安峰,王芹,张凡. 环状RNA hsa_circ_0085576调控微小RNA-498/B细胞特异性莫洛尼鼠白血病病毒整合位点1轴对口腔鳞状细胞癌细胞迁移和侵袭的影响[J]. 国际口腔医学杂志, 2024, 51(1): 60-67.
[7] 吴佳敏,夏斌,杨禾丰,许彪. 癌相关成纤维细胞在口腔鳞状细胞癌微环境中作用的研究进展[J]. 国际口腔医学杂志, 2023, 50(6): 711-717.
[8] 柳江龙, 买买提吐逊·吐尔地. 超声造影在口腔鳞状细胞癌颈部转移性淋巴结诊断中的研究进展[J]. 国际口腔医学杂志, 2023, 50(5): 514-520.
[9] 盛南宁,王珏,南欣荣. 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[J]. 国际口腔医学杂志, 2023, 50(3): 314-320.
[10] 李潭,梁新华. 盘状蛋白结构域受体1在调控恶性肿瘤进展和治疗中的作用[J]. 国际口腔医学杂志, 2023, 50(2): 230-236.
[11] 赵卓平,辛鹏飞,高阳,张彩凤,张宽收,刘青梅. 光热治疗在口腔鳞状细胞癌治疗中的研究进展[J]. 国际口腔医学杂志, 2022, 49(4): 462-470.
[12] 江涵,神应强,陈谦明. 毒蕈碱受体通过Yes相关蛋白信号对口腔鳞状细胞癌生物学行为的实验研究[J]. 国际口腔医学杂志, 2022, 49(2): 138-143.
[13] 熊梦琳,吴龙,马丽,赵今. 转化生长因子-β2促进牙髓干细胞增殖和分化的作用研究[J]. 国际口腔医学杂志, 2021, 48(6): 635-639.
[14] 蒋宇磊,夏斌,饶南荃,杨禾丰,许彪. 外泌体在口腔鳞状细胞癌恶性进展及诊疗应用的研究[J]. 国际口腔医学杂志, 2021, 48(6): 711-717.
[15] 刘娟,陈斌,闫福华. 富血小板血浆和浓缩生长因子对人牙周膜细胞增殖和成骨分化影响的研究[J]. 国际口腔医学杂志, 2021, 48(5): 520-527.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!