TACC2抑制食管鳞状细胞癌的作用及分子机制

It is very important to find new and effective molecular targets for clinical diagnosis and treatment. We found transforming acidic coiled-coil 2 (TACC2) expression level was lower in esophageal squamous cell carcinoma (ESCC) tissues than that in normal tissues through RNA sequencing, bioinformatics analysis and biological verification, and patients with lower TACC2 expression level have poor prognosis through clinical data analysis. To investigate the effect and molecular mechanisms of TACC2 inhibiting ESCC progress and development, we knocked down TACC2 in ESCC cell lines with siRNA, and found that knocking down of TACC2 promotes cell growth, clone formation and cell cycle progress, also decreases protein expression level of p21, which is related to cell cycle regulation. We will try to explore the molecular mechanisms of TACC2 inhibiting cell cycle progress through regulating p21 on transcription, translation and modification after translation levels. As TACC2 belongs to the composed proteins of centrosome spindle, we will confirm the types of chromosome instability induced by knocking down of TACC2 through live cell imaging, SKY and other techniques, will explore the molecular mechanisms of TACC2 inhibits ESCC development and progress through keeping genomic stability. Our research will provide new molecular target for clinical diagnosis and prognosis of ESCC, and new strategy for clinical treatment.

有效的临床诊断与治疗分子靶标对控制食管鳞状细胞癌（ESCC）十分重要。我们前期预试验通过RNA-seq分析及验证，发现酸性卷曲转化相关蛋白（TACC2）在食管鳞状细胞癌（ESCC）组织中表达量低于癌旁正常组织，而且TACC2低表达的患者预后比较差；通过siRNA敲低体外培养ESCC细胞系，发现敲低TACC2促进细胞增殖、克隆形成、细胞周期并下调细胞周期相关蛋白 p21表达。为明确TACC2在ESCC中的抑癌作用及分子机制，我们拟从转录、翻译及翻译后修饰水平研究TACC2调控p21阻滞细胞周期的分子机制。由于TACC2是中心体主轴组成蛋白，异常中心体可以引起染色体不稳定性，我们将通过活细胞摄影、SKY等技术观察敲低TACC2引起染色体不稳定的表型，系统研究TACC2是否通过增加基因组稳定性最终达到抑制肿瘤形成的作用及分子机制。通过以上研究，有望为食管鳞状细胞癌提供新的分子诊断标志和治疗靶点。

有效的临床诊断与治疗分子靶标对控制食管鳞状细胞癌(ESCC)十分重要。我们前期 预试验通过RNA-seq分析及验证，发现酸性卷曲转化相关蛋白(TACC2)在食管鳞状细胞癌 (ESCC)组织中表达量低于癌旁正常组织，而且TACC2低表达的患者预后比较差;通过siR NA敲低体外培养ESCC细胞系，发现敲低TACC2促进细胞增殖、克隆形成、细胞周期并下调 细胞周期相关蛋白 p21表达。为明确TACC2在ESCC中的抑癌作用及分子机制，我们拟从转录、翻译及翻译后修饰水平研究TACC2调控p21阻滞细胞周期的分子机制。由于TACC2是中心体主轴组成蛋白，异常中心体可以引起染色体不稳定性，我们将通过活细胞摄影、SKY 等技术观察敲低TACC2引起染色体不稳定的表型，系统研究TACC2是否通过增加基因组稳定性最终达到抑制肿瘤形成的作用及分子机制。通过以上研究，有望为食管鳞状细胞癌提供 新的分子诊断标志和治疗靶点。