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The mechanisms involved in miR-9 regulated apoptosis in cervical cancer by targeting FOXO3

机译:通过靶向FOXO3涉及miR-9调节宫颈癌细胞凋亡的机制

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摘要

As a seriously global health problem, cervical cancer is a great risk to women which threatens their lives. Approximately 30% patients who received definitive treatment may fail to recover from this disease. Accordingly, there is an imperatively need to explore alternative therapeutic approaches for this disease. Several studies have revealed that miR-9 was a critical regulator during cervical cancer growth. Here, we reported that the miR-9 was overexpressed in cervical tumor tissue and exerted a promoting effect on human cervical cancer cell (SiHa) growth. Both in vitro and in vivo experiments confirmed that miR-9 could stimulate the proliferation and migration of SiHa cells. In contrast, inhibition of miR-9 induced apoptosis in SiHa cells. In addition, dual luciferase reporter system assay verified that there was a strong target relationship between miR-9 and FOXO3. Result of western blot assay showed that the inhibition of miR-9 increased the expression of FOXO3. Moreover, miR-9 regulated FOXO3 downstream proteins Bax, Bcl-2 and p-Akt expressions, which suggesting that miR-9 was involved in the SiHa cells apoptosis. In conclusion, our results suggest that the inhibition of miR-9 could induce apoptosis in cervical cancer by targeting FOXO3 and presented a potential molecular target for the treatment of cervical cancer patients.
机译:作为一个严重的全球健康问题,宫颈癌对威胁他们生活的女性有很大的风险。约有30%的接受过定治疗的患者可能无法从这种疾病中恢复过来。因此,必须有必要探索这种疾病的替代治疗方法。几项研究表明,MIR-9在宫颈癌生长期间是临界调节剂。在这里,我们报道了MIR-9在宫颈肿瘤组织中过表达,并对人宫颈癌细胞(Siha)生长产生了促进作用。体外和体内实验都证实miR-9可以刺激Siha细胞的增殖和迁移。相比之下,抑制miR-9诱导的Siha细胞细胞凋亡。此外,双荧光素酶报告系统测定证实MIR-9和FOXO3之间存在强大的目标关系。 Western印迹测定结果表明,miR-9的抑制增加了FoxO3的表达。此外,miR-9调节的FoxO3下游蛋白Bax,Bcl-2和p-akt表达,表明MiR-9参与了SiHa细胞凋亡。总之,我们的研究结果表明MiR-9的抑制可以通过靶向FOXO3诱导宫颈癌的凋亡,并呈现治疗宫颈癌患者的潜在分子靶标。

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