MicroRNA-337 inhibits cell proliferation and invasion of cervical cancer through directly targeting specificity protein 1

MicroRNA-337 inhibits cell proliferation and invasion of cervical cancer through directly targeting specificity protein 1
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DOI:
10.1177/1010428317711323
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发表时间:
2017-06-22
期刊:
影响因子:
--
通讯作者:
Fu, Chengrui
Fu, Chengrui
中科院分区:
其他
文献类型:
--
作者:
Dong, Wei;Li, Baosheng;Fu, Chengrui

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子宫颈癌是世界上第四大最常见的女性恶性肿瘤。越来越多的研究表明,microrna的异常表达在肿瘤发生和肿瘤发展中起着重要作用,并可能成为包括宫颈癌在内的多种癌症的治疗靶点。因此,鉴定与宫颈癌形成和进展有关的特异性microrna将为宫颈癌患者的治疗提供重要线索。在本研究中,我们旨在检测microRNA-337的表达模式,探讨microRNA-337在宫颈癌恶性表型调控中的生物学作用及其机制。我们发现microRNA-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、国际妇产联合会分期、宫颈癌淋巴结转移呈正相关。microRNA-337的异位表达在体外抑制宫颈癌细胞的增殖和侵袭。此外,特异性蛋白1被鉴定为microRNA-337在宫颈癌中的直接靶点。特异性蛋白1在宫颈癌组织中的表达升高,与microRNA-337表达水平呈负相关。此外,挽救实验显示特异性蛋白1的上调可以挽救microRNA-337对宫颈癌细胞的作用。综上所述,这些发现共同表明,microRNA-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,从而为宫颈癌患者提供了一种潜在的新型潜在治疗靶点。
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.