MicroRNA-183 functions as the tumor suppressor via inhibiting cellular invasion and metastasis by targeting MMP-9 in cervical cancer
MicroRNA-183 functions as the tumor suppressor via inhibiting cellular invasion and metastasis by targeting MMP-9 in cervical cancer
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DOI：
10.1016/j.ygyno.2016.02.006
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发表时间：
2016-04-01
影响因子：
4.7
通讯作者：
Tian, Xiaoyu
中科院分区：
文献类型：
--
作者：
Fan, Dongmei;Wang, Ying;Tian, Xiaoyu
Objective. MicroRNA在宫颈癌的侵袭和转移中起重要作用。发现miR-183抑制或促进多种实体瘤的侵袭和转移。然而，miR-183在宫颈癌中的作用尚不清楚。在这项研究中，miR-183的表达水平在53例宫颈癌和13例正常宫颈组织中通过qRT-PCR进行测量。采用Transwell法检测miR-183的表达对宫颈癌细胞侵袭和转移的影响。我们发现，与正常组织相比，宫颈癌组织中miR-183的表达水平显著下调（0.15 +/- 0.011至0.86 +/- 0.049）。miR-183的异位表达导致宫颈癌细胞系siha和Hela细胞的侵袭和迁移受到抑制（p < 0.0001）。生物信息学分析显示，MMP-9是miR-183的潜在作用靶点，MMP-9在宫颈癌中表达显著上调。此外，双荧光素酶报告基因测定显示MMP-9是miR-183的靶标（p < 0.0001）。MMP-9表达下调后，siha和Hela细胞的侵袭转移能力受到抑制（P < 0.0001）。综上所述，miR-183可能通过靶向MMP-9抑制宫颈癌细胞的侵袭和转移，从而发挥抑癌作用，提示miR-183可能成为宫颈癌治疗的新靶点。(C)2016 Elsevier Inc. All rights reserved.
Objective. MicroRNAs have been reported to play an important role in the invasion and metastasis of cervical cancer. miR-183 was found to inhibit or promote the invasion and metastasis of multiple solid tumors. However, the roles of miR-183 in cervical cancer are unclear.Methods. In this study, miR-183 expression levels were measured in 53 cervical cancer and 13 normal cervical tissues by qRT-PCR. The effects of forced expression of miR-183 on cervical cancer cells invasion and metastasis were investigated using Transwell uncoated or coated with growth factor-reduced Matrigel for migration or invasion assays, respectively.Results. We found that miR-183 expression levels were significantly down-regulated in cervical cancer tissues compared with normal tissues (0.15 +/- 0.011 to 0.86 +/- 0.049). Ectopic expression of miR-183 resulted in the suppression of invasion and migration of cervical cancer cell lines, siha and Hela cells (p < 0.0001). Bioinformatics analysis revealed that MMP-9 was the potential target of miR-183 and it was found that MMP-9 was remarkably up-regulated in cervical cancer. Furthermore, a dual-luciferase reporter assay showed that MMP-9 as a target of miR-183 (p < 0.0001). The invasion and metastasis ability of siha and Hela was suppressed when MMP-9 was down-regulated in vitro (p < 0.0001),Conclusions. In conclusion, our study revealed that miR-183 might be a tumor suppressor via inhibiting the invasion and metastasis of cervical cancer cells through targeting MMP-9, indicating that miR-183 may be a novel potential therapeutic target for cervical cancer. (C) 2016 Elsevier Inc. All rights reserved.