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RASSF9 promotes NSCLC cell proliferation by activating the MEK/ERK axis
Cell Death Discovery ( IF 7 ) Pub Date : 2021-07-31 , DOI: 10.1038/s41420-021-00583-0
Jun Yuan 1 , Qianqian Ju 1, 2, 3 , Jun Zhu 1 , Yun Jiang 1 , Xuechao Yang 1 , Xiaoyu Liu 2, 3 , Jinyu Ma 2, 3 , Cheng Sun 1, 2, 3 , Jiahai Shi 1
Affiliation  

The RAS-associated domain family 9 (RASSF9), a RAS-associated domain family gene, is expressed in a variety of tissues. However, its roles in tumorigenesis, particularly in non-small cell lung cancer (NSCLC), are still not understood well. In the present study, we aimed to examine the potential roles of RASSF9 in NSCLC and the underlying mechanisms. Our data showed that RASSF9 expression was upregulated in NSCLC tissues and cell lines. Increased expression of RASSF9 promotes NSCLC cell proliferation. On the contrary, knockdown of RASSF9 represses cell proliferation. Moreover, the effects of RASSF9 on NSCLC cell proliferation were further confirmed in vivo by using a subcutaneous tumor model. Mechanistically, pharmacological intervention studies revealed that the MEK/ERK axis is targeted by RASSF9 for transducing its regulatory roles on NSCLC cell proliferation. Collectively, our data indicate that RASSF9 plays a key role in tumorigenesis of NSCLC by stimulating tumor cell proliferation, which relies on activation of the MEK/ERK axis. Thus, RASSF9 might be a druggable target for developing novel agents for treating NSCLC.



中文翻译:

RASSF9通过激活MEK/ERK轴促进NSCLC细胞增殖

RAS 相关域家族 9 (RASSF9) 是一种 RAS 相关域家族基因,在多种组织中表达。然而,它在肿瘤发生中的作用,特别是在非小细胞肺癌 (NSCLC) 中的作用,仍然不是很清楚。在本研究中,我们旨在检查 RASSF9 在 NSCLC 中的潜在作用及其潜在机制。我们的数据显示 RASSF9 表达在 NSCLC 组织和细胞系中上调。RASSF9 表达增加促进 NSCLC 细胞增殖。相反,RASSF9 的敲低会抑制细胞增殖。此外,通过使用皮下肿瘤模型在体内进一步证实了RASSF9对NSCLC细胞增殖的影响。从机制上讲,药理干预研究表明,RASSF9 靶向 MEK/ERK 轴以转导其对 NSCLC 细胞增殖的调节作用。总的来说,我们的数据表明 RASSF9 通过刺激肿瘤细胞增殖在 NSCLC 的肿瘤发生中起关键作用,这依赖于 MEK/ERK 轴的激活。因此,RASSF9 可能是开发治疗非小细胞肺癌的新型药物的药物靶点。

更新日期:2021-08-02
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