Ben Wei, Zhang Guangmei, Huang Yangang, Sun Yuhui
Obstetrics and Gynecology Department, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
Cancer Manag Res. 2020 Apr 29;12:2925-2935. doi: 10.2147/CMAR.S234897. eCollection 2020.
Abnormally expressed microRNAs (miRNAs) contribute greatly to the initiation and development of human cancers, including cervical cancer, by regulating the target mRNAs. MiR-27a-3p was up-regulated and acted as an oncogene in multiple cancers. However, the function of miR-27a-3p in cervical cancer has not been fully understood.
The expression of miR-27a-3p in cervical cancer tissues and cell lines was detected by RT-pPCR. MTT assay, colony formation assay and flow cytometry analysis were performed to determine the effects of miR-27a-3p on the growth of cervical cancer cells. The targets of miR-27a-3p were predicted using the miRDB database. Luciferase reporter assay was utilized to confirm the binding between miR-27a-3p and the 3'-untranslated region (UTR) of targets. The expression of target proteins was determined by RT-qPCR and Western blot.
Our results found that miR-27a-3p was overexpressed in cervical cancer tissues and cell lines. Down-regulation of miR-27a-3p significantly inhibited the proliferation, colony formation and promoted apoptosis of cervical cancer cells. Overexpression of miR-27a-3p enhanced the cell proliferation. miR-27a-3p was found to bind the 3'-UTR of F-box and WD repeat domain containing 7 (FBXW7) and resulted in the down-regulation of FBXW7. The up-regulated level of miR-27a-3p was inversely correlated with that of FBXW7 in cervical cancer tissues. Additionally, reintroducing of FBXW7 significantly attenuated the promoting effect of miR-27a-3p on the proliferation of cervical cancer cells.
These results indicated the growth-promoting function of miR-27a-3p in cervical cancer via targeting FBXW7. Our finding suggested the potential application of miR-27a-3p/FBXW7 axis in the diagnosis and treatment of cervical cancer.
异常表达的微小RNA（miRNA）通过调控靶mRNA，在包括宫颈癌在内的人类癌症的发生和发展中发挥着重要作用。MiR-27a-3p在多种癌症中上调并充当癌基因。然而，miR-27a-3p在宫颈癌中的功能尚未完全明确。
通过RT-pPCR检测miR-27a-3p在宫颈癌组织和细胞系中的表达。进行MTT法、集落形成试验和流式细胞术分析，以确定miR-27a-3p对宫颈癌细胞生长的影响。使用miRDB数据库预测miR-27a-3p的靶标。利用荧光素酶报告基因试验证实miR-27a-3p与靶标的3'-非翻译区（UTR）之间的结合。通过RT-qPCR和蛋白质免疫印迹法测定靶蛋白的表达。
我们的结果发现，miR-27a-3p在宫颈癌组织和细胞系中过表达。下调miR-27a-3p可显著抑制宫颈癌细胞的增殖、集落形成并促进其凋亡。miR-27a-3p的过表达增强了细胞增殖。发现miR-27a-3p与含F-盒和WD重复结构域7（FBXW7）的3'-UTR结合，并导致FBXW7下调。在宫颈癌组织中，miR-27a-3p的上调水平与FBXW7的水平呈负相关。此外，重新引入FBXW7可显著减弱miR-27a-3p对宫颈癌细胞增殖的促进作用。
这些结果表明miR-27a-3p通过靶向FBXW7在宫颈癌中具有促进生长的功能。我们的发现提示miR-27a-3p/FBXW7轴在宫颈癌诊断和治疗中的潜在应用。
