TUBA1C在乳腺癌中的表达及其生物学功能探讨
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E-mail:liuchaoying666@163.com

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R737.9

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北京大医公益基金肿瘤学科研能力建设项目(DY-Tumor2022-J001);江苏省科技计划项目(BE2017626)


The expression of TUBA1C and its biological functions in breast cancer
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    摘要:

    目的:本研究旨在系统分析微管基因超家族在乳腺癌中的表达和预后价值,并探究新的功能性微管基因。方法:使用癌症基因组图谱(the Cancer Genome Atlas,TCGA)和Kaplan-Meier plotter数据库分别评估微管基因超家族在乳腺癌中的表达差异和预后价值。通过对乳腺癌组织芯片(tissue microarray,TMA)进行免疫组化(immunochemistry,IHC)染色验证微管蛋白α 家族1c蛋白(tubulin alpha 1c,TUBA1C)的表达和预后价值。在MDA-MB-231和MCF-7乳腺癌细胞中进行了细胞增殖和凋亡分析,进而探究TUBA1C在乳腺癌细胞中的生物学功能。结果:对微管基因超家族的系统分析表明,TUBA1C在乳腺癌中高表达且具有显著的预后价值。IHC 分析表明,相比癌旁正常组织,乳腺癌组织中 TUBA1C 在蛋白水平上高表达(χ2 =6.929,P= 0.008),且 TUBA1C 高表达与较晚的临床分期(χ2 =6.357,P=0.042)和较差的总生存期(overall survival,OS)密切相关(P= 0.021)。此外,单因素(P=0.032)和多因素Cox回归分析(P=0.040)进一步证明了TUBA1C是乳腺癌独立的预后因素。在细胞学水平上,敲低TUBA1C可以显著抑制乳腺癌细胞的增殖并诱导细胞凋亡。结论:TUBA1C是乳腺癌中的潜在癌基因和预后分子标志物。此外,敲低TUBA1C可以抑制乳腺癌细胞增殖并诱导细胞凋亡,TUBA1C亦可作为乳腺癌治疗的潜在靶标。

    Abstract:

    Objective:The current research aims to systematically analyze expression levels and prognostic values of tubulin gene superfamily members in breast cancer and identify novel functional microtubule genes. Methods:The Cancer Genome Atlas(TCGA) and the Kaplan -Meier plotter database were used to define the expression levels and prognostic values of tubulin gene superfamily members in breast cancer,respectively. Expression pattern and prognostic value of tubulin alpha 1c(TUBA1C)was subsequently confirmed on breast cancer tissue microarray(TMA)by immunochemistry(IHC)staining. Moreover,cell viability and apoptosis assays were conducted in MDA - MB - 231 and MCF - 7 breast cancer cells to investigate the functional role of TUBA1C in breast cancer. Results:Systematic analysis of tubulin gene superfamily revealed that TUBA1C was significantly overexpressed and had notable prognostic value in breast cancer. IHC analysis exhibited that the TUBA1C was overexpressed at the protein level in tumor tissues compared with para-tumor tissues(χ2 =6.929,P=0.008),and upregulated TUBA1C was associated with the advanced clinical stage(χ2 = 6.357,P=0.042)and worse overall survival(OS)(P=0.021). In addition,univariate(P=0.032)and multivariate Cox regression analyses (P=0.040)further demonstrated that TUBA1C was an independent prognostic factor in breast cancer. Besides,knockdown of TUBA1C notably suppressed cell proliferation and induced cell apoptosis. Conclusion:These results reveal that TUBA1C is a novel oncogene and a potential prognostic biomarker in breast cancer. Besides,silencing TUBA1C could inhibit breast cancer progression,which could be a potential target for therapy.

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梅杰,许隽颖,王惠宇,顾丁一,刘超英. TUBA1C在乳腺癌中的表达及其生物学功能探讨[J].南京医科大学学报(自然科学版),2022,42(11):1530-1538

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  • 在线发布日期: 2022-11-24
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