miR-188调控TGF-α抑制骨肉瘤细胞增殖与迁移

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

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。

Objective To explore the effects of miR-188 and transforming growth factorα(TGF-α)on the proliferation and migration of osteosarcoma cells.Methods The expressions of miR-188 and TGF-αin 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-αand the expression of interfered TGF-αcould 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-αexpression 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.