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miR-214-3p promotes the proliferation migration and invasion of osteosarcoma cells by targeting CADM1

机译:miR-214-3p通过靶向CADM1促进骨肉瘤细胞的增殖迁移和侵袭

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摘要

Although osteosarcoma (OS) is the most common type of primary bone tumor in adolescents and young adults, its mechanism remains unclear. A previous study by the authors demonstrated that miR-214-3p was upregulated in OS patients. Therefore, the present study aimed to investigate the effect and molecular mechanism of miR-214-3p in OS cells. OS cell lines, U2OS and MNNG/HOS Cl#5, were transiently transfected with miR-214-3p mimics, a control mimic, miR-214-3p inhibitors and a control inhibitor. Subsequent assays revealed that elevated miR-214-3p promoted the proliferative, migratory and invasive abilities of OS cells, while the opposite effects were observed in cells that were transfected with miR-214-3p inhibitors. The interaction between miR-214-3p and cell adhesion molecule 1 (CADM1) 3′untranslated region (UTR) was verified by a dual luciferase assay, which indicated that the relative luciferase activity was decreased in 293T cells that were co-transfected with miR-214-3p mimic and psiCHECK2-CADM1-3′UTR compared with cells that were co-transfected with psiCHECK2-CADM1-3′UTR and control mimic. The knockdown of CADM1 using small-interfering RNA enhanced the proliferative, migratory and invasive abilities of OS cells. Furthermore, downregulated CADM1 expression increased the expression of phosphorylated P44/42 mitogen activated kinase (MAPK). In conclusion, miR-214-3p was able to directly target CADM1 and decrease its expression. This resulted in the activation of the P44/42 MAPK signaling pathway, and thereby promoted the proliferation, migration and invasion of OS cells.
机译:尽管骨肉瘤(OS)是青少年和年轻人中最常见的原发性骨肿瘤类型,但其机制仍不清楚。作者先前的研究表明,OS患者中miR-214-3p上调。因此,本研究旨在研究miR-214-3p在OS细胞中的作用及其分子机制。用miR-214-3p模拟物,对照模拟物,miR-214-3p抑制剂和对照抑制剂瞬时转染OS细胞系U2OS和MNNG / HOS Cl#5。随后的测定表明,升高的miR-214-3p促进了OS细胞的增殖,迁移和侵袭能力,而在用miR-214-3p抑制剂转染的细胞中观察到相反的作用。通过双重荧光素酶试验验证了miR-214-3p与细胞粘附分子1(CADM1)3'非翻译区(UTR)之间的相互作用,这表明在与miR共转染的293T细胞中相对荧光素酶活性降低了-214-3p模拟物和psiCHECK2-CADM1-3'UTR与psiCHECK2-CADM1-3'UTR和对照模拟物共转染的细胞相比。使用小干扰RNA敲低CADM1可增强OS细胞的增殖,迁移和侵袭能力。此外,CADM1表达下调增加了磷酸化的P44 / 42丝裂原活化激酶(MAPK)的表达。总之,miR-214-3p能够直接靶向CADM1并降低其表达。这导致P44 / 42 MAPK信号通路的激活,从而促进OS细胞的增殖,迁移和侵袭。

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