miR-188调控TGF-α抑制骨肉瘤细胞增殖与迁移

doi:10.16352/j.issn.1001-6325.2022.03.003

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (3): 423-428.doi: 10.16352/j.issn.1001-6325.2022.03.003

miR-188调控TGF-α抑制骨肉瘤细胞增殖与迁移

刘伟, 刘晓峰, 赵宝辉^*

河北大学附属医院骨科, 河北保定 071000

收稿日期:2020-10-26 修回日期:2021-07-05 出版日期:2022-03-05 发布日期:2022-03-04
通讯作者: ^* zhaobaohui@aliyun.com
基金资助:
2021年度河北省医学科学研究课题基金(20212125)

miR-188 regulates TGF-α to inhibit proliferation and migration of osteosarcoma cells

LIU Wei, LIU Xiao-feng, ZHAO Bao-hui^*

Department of Orthopaedics, the Affiliated Hospital of Hebei University,Baoding 071000,China

Received:2020-10-26 Revised:2021-07-05 Online:2022-03-05 Published:2022-03-04
Contact: ^* zhaobaohui@aliyun.com

摘要/Abstract

摘要： 目的探索miR-188和转化生长因子α(TGF-α)对骨肉瘤细胞增殖和迁移的影响。方法检测人骨肉瘤组织和癌旁组织中miR-188和TGF-α的表达。TargetScan和双荧光素酶报告基因实验检测TGFA是否为miR-188的靶基因。细胞划痕实验检测骨肉瘤细胞系MG63的迁移能力。构建骨肉瘤裸鼠移植瘤模型并观察对miR-188的影响。结果 miR-188在骨肉瘤组织表达降低(P＜0.01);miR-188能特异性结合TGFA的3′-UTR并负性调控其表达;转染miR-188 mimic能抑制MG63细胞迁移能力,而抑制剂则促进迁移能力,但上调TGF-α和干扰后的表达能减轻抑制作用;在骨肉瘤裸鼠移植瘤模型中,过表达miR-188能产生抑制作用(P＜0.01);而下调miR-188的表达出现相反效果;同时,TGF-α在骨肉瘤组织中表达则明显升高(P＜0.01),降低表达则抑制骨肉瘤增殖。结论 miR-188可能通过靶向下调TGF-α的表达,抑制MG63细胞的增殖与迁移。

关键词: 骨肉瘤, miR-188, TGF-α , 转移, 裸鼠

Abstract: Objective To explore the effects of miR-188 and transforming growth factor α (TGF-α) on the proliferation and migration of osteosarcoma cells. Methods The expressions of miR-188 and TGF-α in human osteosarcoma tissues and adjacent tissues were detected. TGFA was detected as the target gene of miR-188 by TargetScan and dual luciferase reporter gene assay. The migration ability of osteosarcoma cells line MG63 was examined by cell scratch assay. The xenograft model of osteosarcoma was established in nude mice and the effect of miR-188 was observed in a xenograft model of osteosarcoma of nude mice. Results The expression of miR-188 was decreased in osteosarcoma tissues (P＜0.01). miR-188 specifically bound to the 3′-UTR of TGFA and negatively regulated its expression. The transfection of miR-188 mimic could inhibit the migration ability of MG63 cells,while the inhibitor could promoted the migration ability,but the up-regulation of TGF-α and the expression of interfered TGF-α could reduce the inhibition effect. In a nude mouse model of osteosarcoma xenograft,over-expression of miR-188 reduced the inhibitory effect (P＜0.01), while down-regulating the expression of miR-188 expression had the opposite effect. TGF-α expression was significantly increased in osteosarcoma tissues (P＜0.01),while silence protiferation of osteosarcoing was decreased. Conclusions miR-188 may inhibit the proliferation and migration of MG63 cells by targeting the expression of TGF-α.

Key words: osteosarcoma, miR-188, TGF-α, metastasis, nude mouse

中图分类号:

R738

刘伟, 刘晓峰, 赵宝辉. miR-188调控TGF-α抑制骨肉瘤细胞增殖与迁移[J]. 基础医学与临床, 2022, 42(3): 423-428.

LIU Wei, LIU Xiao-feng, ZHAO Bao-hui. miR-188 regulates TGF-α to inhibit proliferation and migration of osteosarcoma cells[J]. Basic & Clinical Medicine, 2022, 42(3): 423-428.

参考文献

[1]Andersen GB, Knudsen A, Hager H, et al. miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts[J]. Mol Oncol, 2018,12:114-131.
[2]Gambarotti M, Tos APD, Vanel D, et al. Osteoblastoma-like osteosarcoma: high-grade or low-grade osteosarcoma?[J]. Histopathology, 2019, 74:494-503.
[3]Dylan CD, Shen S, Francis JH, et al. From genomics to metabolomics: emerging metastatic biomarkers in osteosarcoma[J]. Cancer Metastasis Rev, 2018, 37:719-731.
[4]Wu Y, Sun W, Kong Y, et al. Restoration of microRNA-130b expression suppresses osteosarcoma cell malignant behavior in vitro[J]. Oncol Lett, 2018, 6:97-104.
[5]Hu M, Yuan X, Liu Y, et al. IL-1β-induced NF-κB activation down-regulates miR-506 expression to promotes osteosarcoma cell growth through JAG1[J]. Biomed Pharmacother, 2017, 95: 1147-1155.
[6]Chen G, Zhou H. miRNA-708/CUL4B axis contributes into cell proliferation and apoptosis of osteosarcoma[J]. Eur Rev Med Pharmacol Sci, 2018, 22:5452-5459.
[7]Wang JW, Wu XF, Gu XJ, et al. Exosomal miR-1228 from cancer-associated fibroblasts promotes cell migration and invasion of osteosarcoma by directly targeting SCAI[J]. Oncol Res, 2019, 27:979-986.
[8]赵珂, 王文己, 韩兴文. 相关性miRNAs在骨肉瘤中作用的研究进展[J]. 基础医学与临床, 2018, 38: 1630-1634.
[9]Zhuang M, Qiu X, Dong C, et al. MicroRNA-524 promotes cell proliferation by down-regulating PTEN expression in osteosarcoma[J]. Cancer Cell Int, 2018, 18:114-114.
[10]Li N, Shi H, Zhang L, et al. miR-188 inhibits glioma cell proliferation and cell cycle progression through targeting β-catenin[J]. Oncol Res, 2018, 26:785-794.
[11]Peng Y, Shen X, Jiang H, et al. miR-188-5p suppresses gastric cancer cell proliferation and invasion via targeting ZFP91[J]. Oncol Res, 2018, 27:65-71.
[12]Zhu X, Qiu J, Zhang T, et al. MicroRNA-188-5p promotes apoptosis and inhibits cell proliferation of breast cancer cells via the MAPK signaling pathway by targeting Rap2c[J]. J Cell Physiol, 2020, 235:2389-2402.
[13]Wang M, Zhang H, Yang F, et al. miR-188-5p suppresses cellular proliferation and migration via IL6ST: a potential noninvasive diagnostic biomarker for breast cancer[J]. J Cell Physiol, 2020, 235:4890-4901.
[14]Liu B, Yu Z, Chen X, et al. IL-1β-mediated NF-κB signaling augments the osteosarcoma cell growth through modulating miR-376c/TGF-α axis[J]. Pharmazie, 2017, 72:419-424.
[15]顾国民, 布力布·吉力斯汉, 卢素琼, 等. 肿瘤微环境中Lewis肺腺癌细胞调控巨噬细胞表型转换[J]. 基础医学与临床, 2019, 39: 1252-1258.
[16]Liu X, Chen L, Tian XD, et al. miR-137 and its target TGF-α modulate cell growth and tumorigenesis of non-small cell lung cancer[J]. Eur Rev Med Pharmacol Sci, 2017, 21:511-517.

miR-188调控TGF-α抑制骨肉瘤细胞增殖与迁移

miR-188 regulates TGF-α to inhibit proliferation and migration of osteosarcoma cells

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