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Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

机译:致癌的miR-19a和miR-19b共同调节肿瘤抑制因子MTUS1促进肺癌细胞的增殖和迁移

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MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.
机译:MTUS1(与微管相关的肿瘤抑制基因1)已被鉴定为可以在许多恶性肿瘤中充当肿瘤抑制基因的功能。但是,尚不清楚MTUS1调控的功能和机制。在本研究中,我们报道了miR-19a和miR-19b(miR-19a / b)通过靶向MTUS1促进肺癌细胞的增殖和迁移。首先,MTUS1被证明在肺癌中起着抑癌作用,并与细胞增殖和迁移促进有关。其次,在人类肺癌组织中发现miR-19a / b表达与MTUS1 mRNA /蛋白质表达呈负相关。第三,通过生物信息学分析,MTUS1被鉴定为miR-19a / b的直接靶标。第四,通过细胞转染测定法和荧光素酶报告基因测定法,实验证实了miR-19a / b对肺癌细胞的直接MTUS1调控。最后,miR-19a / b被证明可协同抑制MTUS1表达并协同调节MTUS1表达,从而促进肺癌细胞的增殖和迁移。总之,我们的发现为miR-19a / b的作用提供了第一个线索,miR-19a / b似乎通过下调MTUS1而在肺癌中起着重要作用。

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