[中圖分類號]R739.8[文獻標志碼]A[doi]10.7518/gjkq.2025045
Expressionand function of branch-chain amino acid transaminase1 inoral squamous cellcarcinoma
LiYijie',YuanZhenying',LiMing2
1.Dept.ofentaltheticsgshatomtologicalHospitalangsh,ina;2.gaolal
ofStomatologyCentralSouthUnversityKeyLaboratoryofOralHealthesearchinHunanProvinceangsh410000,China
Supported by:Key Research and Development Project of Hunan Province (2022SK2052)
Correspondence:LiMing,Email: limingq248@163.com
[Abstract]ObjectiveThis study aimed to analyze the expressonand biological functionofbranch-chain amino acid transaminase1(BCAT1) inoral squamous cellcarcinoma (OSCC).MethodsThe expression of BCAT1 in head and neck squamous cellcarcinoma (HNSC)patients and its relationshipwith prognosis were analyzed by bioinformatics.To detect BCAT1 gene expresson in tumor and adjacent tisues,we selected patients with OSCC diagnosed in the Departmentof Oraland Maxillfacial Surgery,XiangyaStomatology Hospital,Central South University from2021to2022. BCATl gene expresson in human OSCCceline and normal oral keratinocytes was analyzed.After plasmid overexpressionor knockdownofBCAT1 gene,the proliferation,migration,and invasionabilityof human OSCCcels were detected by cellproliferation,wound-healing,and invasionassys,respectively.ResultsBCAT1 was highly expressed incancer tisues of HNSC patients in the Cancer Genome Atlas (TCGA)databaseand was one of the independent prognostic factors and potential diagnostic markers of patients.Results ofcellularassays showed thatBCAT1 expression wasupregulated in human OSCCtissues orcelines,therebyregulating theproliferation,migration,and invasionofOSCCcels.Con
clusion BCAT1 gene is a potential therapeutic target for human OSCC.
[Keywords] branch-chain amino acid transaminase 1; oral squamous cell carcinoma; head and neck squamous cell carcinoma; proliferation; migration; invasion
口腔鱗狀細胞癌(oralsquamouscell carcino-ma,OSCC)是頭頸部最常見的癌癥類型之一。在全球癌癥統計(2020)中,男性口腔癌的發病率達到14/10萬,在36種男性癌癥中排名第8位]。雖然綜合序列治療已被廣泛應用,但OSCC患者的5年生存率僅略有提高。由于OSCC患者存在個體差異,患者在影像學或肉眼觀上“無瘤”仍有復發的可能,且復發部位常累及重要器官、神經或血管3]。因此,確定潛在的預后標志物和生物分子靶點對OSCC的治療尤為重要。
支鏈氨基酸轉氨酶1(branch-chainaminoacidtransaminase1,BCAT1)是一種細胞質支鏈轉氨酶,其通過將亮氨酸、異亮氨酸和纈氨酸分解并轉化為相應的支鏈-a酮酸(branch-chain a -ketoa-cid,BCAA),是腫瘤細胞生長的主要能量來源和首選代謝途徑4。此外,有研究發現:BCAT1通過其非酶活性促進腫瘤細胞增殖和遷移。大量研究表明:BCAT1的高表達與乳腺癌、胃癌、食管癌、肺癌、胰腺癌、前列腺癌、卵巢癌、子宮內膜癌、肝癌等多種惡性腫瘤增殖、遷移和侵襲等不良生物學行為有關。BCAT1也被認為是膠質瘤和胃癌發生發展的關鍵癌基因[6,15]。并且,研究[9,14,16-17]發現:BCAT1也是胃癌、宮頸鱗癌和肝細胞癌的預后標志物。總而言之,BCAT1通過其酶活性促進BCAA代謝或(和)非酶活性促進腫瘤進展。然而,BCAT1基因在OSCC中的表達及其生物功能尚不清楚,值得進一步研究。
在本研究中,首先分析了BCAT1基因在OSCC及其配對癌旁組織中的表達。隨后,分析了BCAT1基因在體外OSCC細胞系和正常口腔角質細胞中的表達。在過表達、敲低BCTA1基因后,采用cellcountingkit-8(CCK-8)、劃痕實驗、Tran-swell侵襲實驗分析BCAT1在OSCC細胞中的生物功能,為OSCC的臨床靶向治療提供理論依據。……