RASSF9 promotes NSCLC cell proliferation by activating the MEK/ERK axis.

RASSF9 promotes NSCLC cell proliferation by activating the MEK/ERK axis.
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RASSF9通过激活MEK/ERK轴促进NSCLC细胞增殖

DOI:
10.1038/s41420-021-00583-0
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发表时间:
2021-07-31
影响因子:
7
通讯作者:
Shi J
Shi J
中科院分区:
医学2区
文献类型:
--
作者:
Yuan J;Ju Q;Zhu J;Jiang Y;Yang X;Liu X;Ma J;Sun C;Shi J

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RAS相关结构域家族9(RASSF 9)是RAS相关结构域家族基因,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,仍然没有得到很好的理解。在本研究中,我们旨在研究RASSF 9在NSCLC中的潜在作用及其机制。我们的数据显示RASSF 9在NSCLC组织和细胞系中表达上调。RASSF 9表达增加促进NSCLC细胞增殖。相反,RASSF 9的敲低抑制细胞增殖。此外,RASSF 9对NSCLC细胞增殖的作用通过使用皮下肿瘤模型在体内进一步证实。从机制上讲,药理学干预研究表明,RASSF 9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RASSF 9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,RASSF 9可能是开发用于治疗NSCLC的新药物的药物靶点。
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.
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