Dong Wei, Li Baosheng, Wang Juan, Song Yipeng, Zhang Zicheng, Fu Chengrui
1 Radiation Oncology Department, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, P.R. China.
2 Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, P.R. China.
Tumour Biol. 2017 Jun;39(6):1010428317711323. doi: 10.1177/1010428317711323.
Cervical cancer is the fourth most commonly occurring malignancy in females worldwide. Accumulated studies have demonstrated that the aberrant expression of microRNAs plays important roles in tumorigenesis and tumor development and potentially serves as therapeutic targets in various cancers including cervical cancer. Therefore, the identification of specific microRNAs contributed to cervical cancer formation and progression would provide critical clues for the treatments for patients with this disease. In this study, we aimed to detect microRNA-337 expression pattern and investigate the biological roles of microRNA-337 in the regulation of the malignant phenotypes of cervical cancer and its underlying mechanisms. We found that microRNA-337 expression was significantly downregulated in cervical cancer tissues and cell lines. In addition, its aberrant expression levels were positively correlated with tumor size, International Federation of Gynecology and Obstetrics stage, and lymph node metastasis of cervical cancer. The ectopic expression of microRNA-337 suppressed cell proliferation and invasion of cervical cancer in vitro. Furthermore, specificity protein 1 was identified as a direct target of microRNA-337 in cervical cancer. The expression of specificity protein 1 increased in cervical cancer tissues and negatively correlated with microRNA-337 expression level. Moreover, rescue experiments revealed that upregulation of specificity protein 1 could rescue the effects of microRNA-337 on cervical cancer cells. Taken together, these findings collectively demonstrate that microRNA-337 exerts its tumor-suppressing roles in cervical cancer by directly targeting specificity protein 1, thereby indicating a potential novel potential therapeutic target for patients with cervical cancer.
宫颈癌是全球女性中第四大常见恶性肿瘤。越来越多的研究表明，微小RNA的异常表达在肿瘤发生和发展中起重要作用，并有可能成为包括宫颈癌在内的各种癌症的治疗靶点。因此，鉴定促成宫颈癌形成和进展的特定微小RNA将为该疾病患者的治疗提供关键线索。在本研究中，我们旨在检测微小RNA-337的表达模式，并研究微小RNA-337在调节宫颈癌恶性表型及其潜在机制中的生物学作用。我们发现微小RNA-337在宫颈癌组织和细胞系中的表达明显下调。此外，其异常表达水平与肿瘤大小、国际妇产科联盟分期以及宫颈癌的淋巴结转移呈正相关。微小RNA-337的异位表达在体外抑制了宫颈癌细胞的增殖和侵袭。此外，特异性蛋白1被确定为宫颈癌中微小RNA-337的直接靶点。特异性蛋白1在宫颈癌组织中的表达增加，且与微小RNA-337的表达水平呈负相关。此外，挽救实验表明，上调特异性蛋白1可以挽救微小RNA-337对宫颈癌细胞的影响。综上所述，这些发现共同表明，微小RNA-337通过直接靶向特异性蛋白1在宫颈癌中发挥其肿瘤抑制作用，从而为宫颈癌患者指明了一个潜在的新型治疗靶点。
