Rig-G is a growth inhibitory factor of lung cancer cells that suppresses STAT3 and NF-κB.

Rig-G is a growth inhibitory factor of lung cancer cells that suppresses STAT3 and NF-κB.
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Rig-G 是一种肺癌细胞生长抑制因子,可抑制 STAT3 和 NF-κB

DOI:
10.18632/oncotarget.11797
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发表时间:
2016-10-04
期刊:
影响因子:
--
通讯作者:
Wu K
Wu K
中科院分区:
其他
文献类型:
--
作者:
Li D;Sun J;Liu W;Wang X;Bals R;Wu J;Quan W;Yao Y;Zhang Y;Zhou H;Wu K

文献摘要

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维甲酸诱导的G(Rig-G)基因的表达,全反式维甲酸(ATRA)诱导的基因,观察到在多种癌细胞,包括肺癌细胞。然而,Rig-G是否是肺癌的肿瘤抑制因子尚不清楚。在这里,我们发现Rig-G的异位表达可以导致肺癌细胞增殖的显著降低,从而抑制肿瘤生长。Rig-G敲低导致细胞增殖适度增加,以及赋予集落形成增加。此外,癌细胞的转录组和途径分析揭示了Rig-G对各种生长信号传导途径的根本影响,包括NF-κB途径。Rig-G通过抑制肺癌细胞中的STAT 3来抑制NF-κB活性。miR 21和miR 181 B-1的下调以及随后的PTEN/Akt和CYLD/IκB信号传导轴的激活导致NF-κB活性降低,这是维持Rig-G抑制肿瘤作用所必需的。我们的研究结果有助于更好地理解Rig-G的抗肿瘤作用机制,并为肺癌治疗提供新的策略。
The expression of the retinoic acid-induced G (Rig-G) gene, an all trans retinoic acid (ATRA)-inducible gene, was observed in multiple cancer cells, including lung cancer cells. However, whether Rig-G is a tumor suppressor in lung cancer is unknown. Here, we found that ectopic expression of Rig-G can lead to a significant decrease in proliferation of lung cancer cells, resulting in an inhibition of tumor growth. Rig-G knockdown results in a modest increase in cell proliferation, as well as confers an increase in colony formation. Furthermore, transcriptome and pathway analyses of cancer cells revealed a fundamental impact of Rig-G on various growth signaling pathways, including the NF-κB pathway. Rig-G inhibits NF-κB activity by suppressing STAT3 in lung cancer cells. The downregulation of miR21 and miR181b-1 and subsequent activation of PTEN/Akt and CYLD/IκB signaling axis leading to decreased NF-κB activity required to maintain the tumor-inhibiting effect of Rig-G.. Our findings contribute to a better understanding of the antitumor effect mechanism of Rig-G, as well as offer a novel strategy for lung cancer therapy.