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miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma
Cancer Letters ( IF 9.7 ) Pub Date : 2020-03-03 , DOI: 10.1016/j.canlet.2020.02.035
C Molist 1 , N Navarro 1 , I Giralt 1 , P Zarzosa 1 , G Gallo-Oller 1 , G Pons 1 , A Magdaleno 1 , L Moreno 2 , G Guillén 3 , R Hladun 2 , M Garrido 4 , A Soriano 1 , M F Segura 1 , J Sánchez de Toledo 5 , S Gallego 5 , J Roma 1
Affiliation  

The prognosis of patients with metastatic rhabdomyosarcoma (RMS), the most common type of soft tissue sarcoma in children, is poor and no strategies have been identified to improve their dismal prognosis. Alpha-9 integrin (ITGA9) plays a particularly crucial role in cancer progression and invasiveness. Despite the consensus on the remarkable pro-oncogenic potential of this protein, the miRNA-mediated regulation of ITGA9 has barely been studied to date. In the present study, miR-7 and miR-324-5p were selected as the best candidates after a screening to find ITGA9 regulators, and their effects on cell proliferation and invasion in RMS are described and characterized for the first time. Interestingly, the overexpression of both miRNA produced a clear impairment of cell proliferation, while miR-7 also induced a remarkable drop in cell invasion. Furthermore, the stable overexpression of both miRNA was found to reduce tumor growth in orthotopic RMS models and miR-7 was able to impair metastatic lung colonization. Consequently, we conclude that miR-7 and miR-324-5p show anti-oncogenic and anti-metastatic potential, thereby opening up the possibility of being used as novel therapeutic tools to avoid RMS progression.



中文翻译:

miRNA-7 和 miRNA-324-5p 调节 alpha9-Integrin 表达并在横纹肌肉瘤中发挥抗癌作用

转移性横纹肌肉瘤 (RMS) 是儿童中最常见的软组织肉瘤类型,其预后很差,并且尚未确定改善其糟糕预后的策略。Alpha-9 整合素 (ITGA9) 在癌症进展和侵袭中起着特别重要的作用。尽管对该蛋白质显着的促癌潜力达成了共识,但迄今为止几乎没有研究过 miRNA 介导的 ITGA9 调节。在本研究中,miR-7 和 miR-324-5p 经过筛选以寻找 ITGA9 调节剂后被选为最佳候选者,并首次描述和表征了它们对 RMS 中细胞增殖和侵袭的影响。有趣的是,两种 miRNA 的过表达都对细胞增殖产生了明显的损害,而 miR-7 也诱导了细胞侵袭的显着下降。此外,发现两种 miRNA 的稳定过表达可减少原位 RMS 模型中的肿瘤生长,并且 miR-7 能够损害转移性肺定植。因此,我们得出结论,miR-7 和 miR-324-5p 显示出抗致癌和抗转移的潜力,从而开辟了用作避免 RMS 进展的新型治疗工具的可能性。

更新日期:2020-03-03
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