Department of Obstetrics and Gynecology, Chongqing General Hospital, Chongqing, China.
Bioengineered. 2022 Mar;13(3):6955-6965. doi: 10.1080/21655979.2022.2036901.
Cervical cancer represents one of the most important female genital cancers. Cervical squamous cell carcinoma (CESC) accounts for about 90% of all cervical malignancies and the prognosis are unsatisfied. Here we aimed to investigate the clinical relevance of metallothionein-like 5 (MTL5), a novel metallothionein-like protein, in CESC. RT-qPCR and immunohistochemistry staining showed that MTL5 was upregulated in CESC tissues than nontumorous cervix tissues, which is consistent with the data from TCGA database. Kaplan-Meier survival analysis revealed that higher MTL5 can help predict worse prognosis. In addition, Cox hazard regression analysis verified an independent predictive role of MTL5 in CESC. To further investigate the involvement of MTL5 in CESC, we conducted knockdown experiments in two CESC cell lines. As a result, silencing MTL5g significantly inhibited proliferation of CESC cells. Finally, we validated that silencing MTL5 can suppress CESC tumor growth in vivo using the mice subcutaneous xenografts model. Taken together, higher MTL5 indicates worse survival of CESC after surgical resection. Targeting MTL5 represents a potential therapy of CESC by inhibiting tumor growth, which deserves further investigations.
宫颈癌是女性生殖系统最重要的恶性肿瘤之一。宫颈鳞状细胞癌(CESC)约占所有宫颈癌的 90%,其预后并不令人满意。本研究旨在探讨金属硫蛋白样蛋白 5(MTL5)在宫颈鳞癌中的临床相关性。RT-qPCR 和免疫组织化学染色结果显示,MTL5 在宫颈鳞癌组织中的表达高于非肿瘤宫颈组织,这与 TCGA 数据库中的数据一致。Kaplan-Meier 生存分析显示,MTL5 表达水平越高,提示预后越差。此外,Cox 风险回归分析验证了 MTL5 在宫颈鳞癌中的独立预测作用。为了进一步探讨 MTL5 在宫颈鳞癌中的作用,我们在两种宫颈鳞癌细胞系中进行了敲低实验。结果表明,沉默 MTL5g 可显著抑制宫颈鳞癌细胞的增殖。最后,我们通过小鼠皮下移植瘤模型验证了沉默 MTL5 可抑制宫颈鳞癌肿瘤的生长。综上所述,MTL5 表达水平升高提示宫颈鳞癌患者术后生存不良。抑制 MTL5 可能成为治疗宫颈鳞癌的一种潜在方法,值得进一步研究。