Li Hong-Lin, Sun Jun-Jie, Ma Hui, Liu Shen-Jia, Li Na, Guo Su-Jie, Shi Yang, Xu Yan-Ying, Qi Zhi-Ying, Wang Yu-Quan, Wang Fang, Guo Rui-Meng, Liu Dong, Xue Feng-Xia
Department of Obstetrics and Gynecology, The Secondary Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Oncol Lett. 2019 Oct;18(4):3792-3802. doi: 10.3892/ol.2019.10694. Epub 2019 Jul 31.
The present study focused on exploring the inhibitory mechanism of microRNA (miR)-23a in endometrial cancer. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to investigate miR-23a expression in endometrial tissues and endometrial cancer cells. A colony formation assay using crystal violet staining was performed to compare cell proliferation, while wound-healing and Transwell assays were performed to compare cell migration and invasion. Subsequently, bioinformatics and a luciferase reporter gene assay were used to investigate the effect of miR-23a on homeobox homolog 1 (SIX1) expression, and the biological function of SIX1 was analyzed. Additionally, a nude mouse tumorigenicity assay was performed to test the inhibitory effect of miR-23a and Taxol therapy in endometrial cancer. Finally, immunohistochemistry and RT-qPCR were used to explore the association between miR-23a and SIX1 expression in endometrial cancer tissues. miR-23a was underexpressed in endometrial cancer tissues compared with in para-carcinoma tissues, and the overexpression of miR-23a inhibited proliferation and invasion of endometrial cancer cells. Furthermore, SIX1 was demonstrated to be a downstream target of miR-23a, and miR-23a reduced SIX1 expression. Additionally, SIX1 inversely promoted cell proliferation, migration and invasion. In addition, the effects of reduced cell proliferation and increased cell invasion following miR-23a overexpression could be reversed by adding SIX1 to culture. Furthermore, the inhibitory effect of miR-23a and Taxol therapy, which reduced SIX1 expression in endometrial cancer, was demonstrated . Finally, a negative association between miR-23a and SIX1 expression was demonstrated in endometrial cancer tissues. The results of the present study revealed that miR-23a may inhibit endometrial cancer development by targeting SIX1.
本研究聚焦于探索微小RNA（miR）-23a在子宫内膜癌中的抑制机制。采用逆转录定量聚合酶链反应（RT-qPCR）检测miR-23a在子宫内膜组织和子宫内膜癌细胞中的表达。进行结晶紫染色的集落形成试验以比较细胞增殖，同时进行伤口愈合试验和Transwell试验以比较细胞迁移和侵袭。随后，利用生物信息学和荧光素酶报告基因试验研究miR-23a对同源盒蛋白1（SIX1）表达的影响，并分析SIX1的生物学功能。此外，进行裸鼠致瘤试验以检测miR-23a和紫杉醇治疗对子宫内膜癌的抑制作用。最后，采用免疫组织化学和RT-qPCR探讨miR-23a与子宫内膜癌组织中SIX1表达之间的关联。与癌旁组织相比，miR-23a在子宫内膜癌组织中表达下调，miR-23a过表达抑制子宫内膜癌细胞的增殖和侵袭。此外，SIX1被证明是miR-23a的下游靶点，miR-23a降低SIX1的表达。另外，SIX1反过来促进细胞增殖、迁移和侵袭。此外，在培养物中添加SIX1可逆转miR-23a过表达后细胞增殖减少和细胞侵袭增加的作用。此外，证实了miR-23a和紫杉醇治疗可降低子宫内膜癌中SIX1的表达，具有抑制作用。最后，在子宫内膜癌组织中证实了miR-23a与SIX1表达呈负相关。本研究结果表明，miR-23a可能通过靶向SIX1抑制子宫内膜癌的发展。
