Novel cytoplasmic lncRNA IKBKBAS promotes lung adenocarcinoma metastasis by upregulating IKKβ and consequential activation of NF-κB signaling pathway.
Novel cytoplasmic lncRNA IKBKBAS promotes lung adenocarcinoma metastasis by upregulating IKKβ and consequential activation of NF-κB signaling pathway.
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DOI：
10.1038/s41419-021-04304-4
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发表时间：
2021-10-26
影响因子：
9
通讯作者：
Han B
中科院分区：
文献类型：
--
作者：
Xing Y;Lin Y;Zhang Y;Hu J;Liu J;Tian Y;Zhao J;Chen W;Han B
NF-κB信号通路是炎症和肿瘤之间的重要环节。新的证据表明，长链非编码RNA（lncRNA）参与了NF-κB的调节异常。本文报道了一种新的lncRNA IKBKBAS，它通过上调NF-κB信号通路的关键成员IKKβ，激活肺腺癌（LUAD）中的NF-κB，从而促进LUAD的体内外转移。上调的IKBKBAS通过与IKKβ mRNA竞争结合miR-4741，作为竞争性内源性RNA（ceRNA）发挥作用，从而导致IKKβ上调和激活，并最终激活NF-κB。LUAD中IKBKBAS的异常升高主要是由于靶向IKBKBAS的miR-512- 5 p的极度减少所致。此外，我们还发现了NF-κB和IKBKBAS之间存在一个正反馈环，在这个正反馈环中，IKBKBAS过表达诱导的NF-κB活化可以通过结合IKBKBAS启动子中的κB位点来促进IKBKBAS的转录。我们的研究表明，IKBKBAS通过上调IKKβ的表达，参与NF-κB信号通路的激活，有望成为LUAD治疗的新靶点。
NF-κB signaling pathway is a critical link between inflammation and cancer. Emerging evidence suggested that long non-coding RNAs (lncRNAs) were involved in dysregulation of NF-κB. Herein, we reported a novel lncRNA IKBKBAS that activated NF-κB in lung adenocarcinoma (LUAD) by upregulating IKKβ, a key member of NF-κB signaling pathway, thereby promoting the metastasis of LUAD both in vitro and in vivo. The upregulated IKBKBAS functioned as a competing endogenous RNA (ceRNA) via competing with IKKβ mRNA for binding miR-4741, consequently leading to upregulation and activation of IKKβ, and ultimately activation of NF-κB. The abnormally elevated IKBKBAS in LUAD was mainly resulted from the extremely decrease of miR-512-5p that targeting IKBKBAS. Furthermore, we identified a positive feedback loop between NF-κB and IKBKBAS, in which NF-κB activation induced by overexpression of IKBKBAS could promote the transcription of IKBKBAS by binding the κB sites within IKBKBAS promoter. Our studies revealed that IKBKBAS was involved in the activation of NF-κB signaling by upregulating the expression of IKKβ, which made it serve as a potential novel target for therapies to LUAD.
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影响因子：
4.5
作者：
Brodsky, AS;Silver, PA
通讯作者：
Silver, PA
DOI：
10.2741/3782
发表时间：
2011-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Chen W;Li Z;Bai L;Lin Y
通讯作者：
Lin Y
影响因子：
4
作者：
Chen, Wenshu;Wang, Xia;Bai, Lang;Liang, Xiaomin;Zhuang, Jianguo;Lin, Yong
通讯作者：
Lin, Yong
影响因子：
5.2
作者：
Chu, Kaili;Gao, Guanghui;Zhou, Caicun
通讯作者：
Zhou, Caicun
影响因子：
6.1
作者：
Li, Miao-Miao;Dong, Chang-Xian;Sun, Zheng-Wei
通讯作者：
Sun, Zheng-Wei