Sun Jun-Jie, Li Hong-Lin, Ma Hui, Shi Yang, Yin Li-Rong, Guo Su-Jie
Department of Gynecology, The Secondary Hospital of Tianjin Medical University, No. 23 Pingjiang Road, Hexi District, Tianjin, 300211 China.
Cell Biosci. 2019 Sep 18;9:75. doi: 10.1186/s13578-019-0340-9. eCollection 2019.
Cervical cancer is the most common gynecological malignancy with low terminal cure rate, and therefore new therapeutic targets are urgently needed to combat this disease. SMYD2, as an oncogene, is abnormal highly expressed in multiple types of tumors and further affects the occurrence and development, but the potential correlations between SMYD2 expression and cervical cancer progression is still unclear.
We first used the bioinformatics website to screen the data of cervical cancer in (The Cancer Genome Atlas) TCGA and survival analysis was used to find the different survival rates in the SMYD2 high expression group and low expression group. Through immunohistochemistry, the association between SMYD2 expression and clinical-pathological features of cervical cancer patients was further evaluated. Quantitative PCR and Immunoblot were applied to investigate the relative mRNA and protein expression levels, respectively. In vivo and in vitro experiments were performed to explore the function of SMYD2 in cancer progression.
We first found a high expression of SMYD2 in cervical cancer, and survival analysis found that the poorer survival rate in the SMYD2 high expression group than that in the low expression group. Herein, our study demonstrated that the expression of SMYD2 in patients with cervical cancer was associated with FIGO stage, tumor size and further correlated with poor prognosis. Our data further showed that the inhibition of SMYD2 expression in cervical cancer cell line Caski and Siha could dramatically block the proliferation of cervical cancer cells. Additionally, SMYD2-shRNA lentivirus infected remarkably inhibited tumorigenesis in mice compared with the scramble group.
Taken together, this study provides strong evidence of the involvement of SMYD2 in cervical cancer growth and indicates that it could have high potential as a therapeutic target of cervical cancer.
宫颈癌是最常见的妇科恶性肿瘤,终末期治愈率低,因此迫切需要新的治疗靶点来对抗这种疾病。SMYD2作为一种癌基因,在多种类型的肿瘤中异常高表达,并进一步影响肿瘤的发生和发展,但SMYD2表达与宫颈癌进展之间的潜在关联仍不清楚。
我们首先使用生物信息学网站筛选(癌症基因组图谱)TCGA中宫颈癌的数据,并使用生存分析来找出SMYD2高表达组和低表达组的不同生存率。通过免疫组织化学,进一步评估SMYD2表达与宫颈癌患者临床病理特征之间的关联。分别应用定量PCR和免疫印迹法研究相对mRNA和蛋白表达水平。进行体内和体外实验以探索SMYD2在癌症进展中的作用。
我们首先发现宫颈癌中SMYD2高表达,生存分析发现SMYD2高表达组的生存率低于低表达组。在此,我们的研究表明,宫颈癌患者中SMYD2的表达与国际妇产科联盟(FIGO)分期、肿瘤大小相关,并进一步与预后不良相关。我们的数据进一步表明,抑制宫颈癌细胞系Caski和Siha中SMYD2的表达可显著阻断宫颈癌细胞的增殖。此外,与对照组相比,SMYD2-shRNA慢病毒感染显著抑制了小鼠的肿瘤发生。
综上所述,本研究提供了强有力的证据证明SMYD2参与宫颈癌生长,并表明它作为宫颈癌的治疗靶点具有很大潜力。