miR-4306通过下调SATB2表达抑制骨肉瘤细胞增殖、迁移与侵袭

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摘要目的: 研究miR-4306在骨肉瘤细胞中的表达及其对骨肉瘤细胞生物学行为的影响。方法: 选取人成骨细胞hFOB 1.19和骨肉瘤细胞Saos-2、MNNG/HOS CI #5，采用qRT-PCR检测miR-4306表达水平。将miR-4306 mimics和阴性对照分别转染至骨肉瘤细胞Saos-2和MNNG/HOS CI #5，采用CCK-8法和克隆形成实验检测细胞增殖，Transwell实验检测细胞迁移及侵袭，蛋白质免疫印迹检测细胞内上皮间质转化（epithelialmesenchymal transition, EMT）标志蛋白表达水平。通过在线靶基因预测网站Targetscan、Starbase预测miR-4306靶基因可能为富含AT序列特异性结合蛋白2（special ATrich sequencebinding protein 2, SATB2），荧光素酶报告系统鉴定靶向关系。将miR4306 mimics、LVSATB2共转染至骨肉瘤细胞中，检测细胞增殖、迁移、侵袭以及EMT标志蛋白表达水平变化。结果: 与人成骨细胞hFOB 1.19比较，骨肉瘤细胞Saos2、MNNG/HOS CI #5中miR-4306表达明显降低（P均＜0.01）。转染miR-4306 mimics后，骨肉瘤细胞增殖、迁移、侵袭能力下降，N-钙黏蛋白、血管内皮生长因子表达水平显著降低，E钙黏蛋白表达水平显著升高（P＜0.05或＜0.01）。SATB2是miR-4306下游的直接靶标；与miR-4306 mimics+LV-NC组比较，miR-4306 mimics+LV-SATB2组部分逆转miR-4306对骨肉瘤细胞增殖、侵袭、迁移和EMT的影响。结论: miR-4306在骨肉瘤细胞中呈低表达，其可通过下调SATB2表达抑制骨肉瘤细胞增殖、迁移、侵袭和EMT。

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Abstract：Objective： To study the expression of miR4306 in osteosarcoma cells and its effect on the biological behavior of osteosarcoma cells. Methods： Human osteoblast hFOB 1.19 and osteosarcoma cells Saos2, MNNG/HOS CI #5 were selected, and qRTPCR was used to detect the expression level of miR4306. miR4306 mimics and negative control were transfected into osteosarcoma cells Saos2 and MNNG/HOS CI #5, respectively; and cell proliferation was detected by CCK8 assay and colony formation assay, cell migration and invasion were detected by Transwell assay, and Western blotting was used to detect the expression levels of epithelialmesenchymal transition （EMT） marker proteins. The online target gene prediction websites Targetscan and Starbase predicted that the target gene of miR4306 might be special ATrich sequencebinding protein 2 （SATB2）, and the luciferase reporter system was used to identify the target relationship. miR4306 mimics and LVSATB2 were cotransfected into osteosarcoma cells, and the changes in cell proliferation, migration, invasion and EMT marker protein expression levels were detected. Results： Compared with human osteoblast hFOB 1-19, the expression of miR-4306 in osteosarcoma cells Saos-2 and MNNG/HOS CI #5 was significantly decreased （both P＜0.01）. After transfection with miR-4306 mimics, the proliferation, migration and invasion abilities of osteosarcoma cells were significantly decreased, the expression levels of Ncadherin and vascular endothelial growth factor were significantly decreased, and the expression level of Ecadherin was greatly increased （P<0.05 or<0.01）. SATB2 is a direct downstream target of miR-4306; compared with the miR-4306 mimics+LV-NC group, the miR-4306 mimics+LV-SATB2 group partially reversed the effects of miR-4306 on osteosarcoma cell proliferation, invasion, migration and EMT. Conclusion： miR-4306 is lowly expressed in osteosarcoma cells, and it could inhibit osteosarcoma cell proliferation, migration, invasion and EMT by downregulating the expression of SATB2.

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收稿日期: 2021-12-21

基金资助: 福建省卫生计生委医学创新课题（2018-CXR-2）

通讯作者: 汤发强（通讯作者），副教授，硕士生导师，E-mail:tfqlove@163.com

作者简介: 李书林（1995—），男，硕士研究生

引用本文:

李书林，廖艺琳，周子杰，等.. miR-4306通过下调SATB2表达抑制骨肉瘤细胞增殖、迁移与侵袭[J]. 江苏大学学报:医学版, 2023, 33(01): 42-48. LI Shulin1,2, LIAO Yilin3, ZHOU Zijie4, XIAO Zhengwei1, SU Lingbo1, LI Junjie1, LAN Qing1, CHEN Mingdi1, GUO Huiling1,2, YAN Laipeng1,2, TANG Faqiang1,2. miR4306 inhibits the proliferation, migration and invasion of osteosarcoma cells by down-regulating the expression of special AT-rich sequence-binding protein 2

. Journal of Jiangsu University(Medicine Edition), 2023, 33(01): 42-48.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2023/V33/I01/42

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