Wang Shanzong, Gao Baohong, Yang Hailin, Liu Xuejian, Wu Xia, Wang Weijuan
Department of Pathology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China.
Department of Gynecology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China.
Oncol Lett. 2019 Aug;18(2):1475-1482. doi: 10.3892/ol.2019.10403. Epub 2019 May 27.
Numerous studies have identified the dysregulation of microRNAs (miRNAs) in cervical cancer, and dysregulated miRNAs are involved in regulating a number of tumour- associated biological behaviours. Therefore, investigating the roles of cervical cancer-associated miRNAs and the underlying molecular mechanisms is essential for the development of novel diagnostic biomarkers and effective therapeutic targets. MicroRNA-432 (miR-432) dysregulation has been revealed to be implicated in the carcinogenesis and progression of a number of types of human cancer. However, the effects and underlying molecular mechanisms of miR-432 in cervical cancer have yet to be elucidated. In the present study, miR-432 expression was determined using reverse transcription-quantitative polymerase chain reaction. The results revealed that miR-432 was expressed at low levels in cervical cancer tissues and cell lines. Decreased miR-432 expression was significantly associated with the International Federation of Gynecology and Obstetrics stage, myometrium invasion and lymph node metastasis of patients with cervical cancer. Following transfection with miR-432 mimic, the expression of miR-432 was significantly upregulated in cervical cancer cells. Upregulation of miR-432 expression restricted the proliferation and invasion of cervical cancer cells. Bioinformatics analysis followed by luciferase reporter assays revealed that fibronectin 1 (FN1) was a direct target gene of miR-432 in cervical cancer cells. In addition, FN1 was upregulated in cervical cancer tissues and was inversely correlated with miR-432 levels. Furthermore, miR-432 upregulation decreased the expression levels of FN1 in cervical cancer cells at the mRNA and protein levels. Furthermore, silencing of FN1 could stimulate the tumour suppressor effects of miR-432 upregulation in cervical cancer cells. In addition, restored FN1 expression neutralized the effects of miR-432 overexpression in cervical cancer cells. The results of the present study indicate that miR-432 is a tumour suppressor that can restrain the aggressive phenotype of cervical cancer cells by directly targeting FN1, suggesting that this miRNA may be developed as an effective therapeutic strategy for patients with cervical cancer.
大量研究已确定宫颈癌中微小RNA（miRNA）的失调，且失调的miRNA参与调控多种肿瘤相关生物学行为。因此，研究宫颈癌相关miRNA的作用及其潜在分子机制对于开发新型诊断生物标志物和有效的治疗靶点至关重要。微小RNA-432（miR-432）失调已被揭示与多种类型人类癌症的发生和进展有关。然而，miR-432在宫颈癌中的作用及其潜在分子机制尚未阐明。在本研究中，采用逆转录定量聚合酶链反应测定miR-432表达。结果显示，miR-432在宫颈癌组织和细胞系中低表达。miR-432表达降低与宫颈癌患者的国际妇产科联盟分期、肌层浸润和淋巴结转移显著相关。用miR-432模拟物转染后，宫颈癌细胞中miR-432的表达显著上调。miR-432表达上调限制了宫颈癌细胞的增殖和侵袭。生物信息学分析及荧光素酶报告基因检测显示，纤连蛋白1（FN1）是宫颈癌细胞中miR-432的直接靶基因。此外，FN1在宫颈癌组织中上调，且与miR-432水平呈负相关。此外，miR-432上调在mRNA和蛋白水平降低了宫颈癌细胞中FN1的表达水平。此外，沉默FN1可增强miR-432上调对宫颈癌细胞的肿瘤抑制作用。此外，恢复FN1表达可抵消miR-432过表达对宫颈癌细胞的影响。本研究结果表明，miR-432是一种肿瘤抑制因子，可通过直接靶向FN1抑制宫颈癌细胞的侵袭性表型，提示该miRNA可能被开发为宫颈癌患者的有效治疗策略。
