Zhou Wenbin, Zhang Yayuan, Zhong Caineng, Hu Jintao, Hu Hong, Zhou Dongxian, Cao MeiQun
Department of Breast Surgery, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China,
Department of Pathology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, China.
Cancer Manag Res. 2018 Sep 20;10:3687-3696. doi: 10.2147/CMAR.S175470. eCollection 2018.
Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase, has been implicated in autoimmune diseases. Dysregulation of TRIM21 contributes to the progression of human malignancies, but its role and clinical significance in breast cancer remain unclear.
The expression of TRIM21 was examined by quantitative real-time PCR, Western blot, and immunohistochemistry. The role of TRIM21 in the progression of breast cancer was determined using in vitro and in vivo models. The upstream regulation of TRIM21 was investigated by luciferase reporter assay.
Here, we showed that TRIM21 expression in breast cancer tissues was decreased at both the mRNA and protein levels in comparison to that in nontumorous tissues. TRIM21 expression was closely associated with tumor size, estrogen receptor, human epidermal growth factor receptor 2, and clinical stage. Low TRIM21 expression was correlated with poor overall and disease-free survival in two independent cohorts containing 1,219 patients with breast cancer. A multivariate Cox regression model suggested TRIM21 as an independent factor for overall survival. In vitro data revealed that TRIM21 expression was suppressed by miR-494-3p directly targeting the 3' untranslated region of TRIM21. Overexpression of TRIM21 impeded cell proliferation and tumor growth in breast cancer, whereas TRIM21 depletion enhanced these capacities.
Collectively, our findings indicate that TRIM21 serves as a potential prognostic biomarker and functions as a tumor suppressor in breast cancer.
含三联基序蛋白21（TRIM21）是一种E3泛素连接酶，与自身免疫性疾病有关。TRIM21的失调促进人类恶性肿瘤的进展，但其在乳腺癌中的作用和临床意义仍不清楚。
采用定量实时PCR、蛋白质免疫印迹和免疫组织化学检测TRIM21的表达。利用体外和体内模型确定TRIM21在乳腺癌进展中的作用。通过荧光素酶报告基因检测研究TRIM21的上游调控。
我们发现，与非肿瘤组织相比，乳腺癌组织中TRIM21的mRNA和蛋白质水平均降低。TRIM21表达与肿瘤大小、雌激素受体、人表皮生长因子受体2及临床分期密切相关。在两个包含1219例乳腺癌患者的独立队列中，低TRIM21表达与总体生存率和无病生存率低相关。多变量Cox回归模型表明TRIM21是总体生存的独立因素。体外数据显示，miR-494-3p直接靶向TRIM21的3'非翻译区可抑制TRIM21表达。TRIM21过表达可抑制乳腺癌细胞增殖和肿瘤生长，而TRIM21缺失则增强这些能力。
总体而言，我们的研究结果表明，TRIM21作为一种潜在的预后生物标志物，在乳腺癌中发挥肿瘤抑制作用。
