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The novel long noncoding RNA AU021063, induced by IL-6/Arid5a signaling, exacerbates breast cancer invasion and metastasis by stabilizing Trib3 and activating the Mek/Erk pathway
Cancer Letters ( IF 9.7 ) Pub Date : 2021-08-10 , DOI: 10.1016/j.canlet.2021.08.004
Kishan Kumar Nyati 1 , Shigeru Hashimoto 1 , Shailendra Kumar Singh 2 , Murat Tekguc 3 , Hozaifa Metwally 1 , Yu-Chen Liu 4 , Daisuke Okuzaki 5 , Yohannes Gemechu 1 , Sujin Kang 1 , Tadamitsu Kishimoto 1
Affiliation  

Interleukin (IL-6) is a pleotropic cytokine with both tumor-promoting and -inhibitory effects on breast cancer growth. However, the mechanisms governing the outcome of IL-6 on cancer progression remain to be clarified. Our study unraveled a novel long noncoding RNA (lncRNA) AU021063 downstream of IL-6 signaling. We found that IL-6 induced the expression of AU021063 predominantly in breast cancer compared to other cancer types. Mechanistically, IL-6 induced AT-rich interactive domain 5a (Arid5a) expression, which promotes the transcription of AU021063. In turn, AU021063 promotes breast cancer metastasis through stabilizing tribbles homolog 3 (Trib3) and activating Mek/Erk signaling pathway. Genetic ablation of either Arid5a, AU021063 or Trib3 abolished breast cancer metastasis in vitro and in vivo. Overall, our study highlights the importance of IL-6-Arid5a-AU021063 axis in regulating breast cancer invasiveness and metastasis, which may provide potential novel therapeutics for breast cancer.



中文翻译:

由 IL-6/Arid5a 信号传导诱导的新型长链非编码 RNA AU021063 通过稳定 Trib3 和激活 Mek/Erk 通路加剧乳腺癌的侵袭和转移

白细胞介素 (IL-6) 是一种多效性细胞因子,对乳腺癌的生长具有促肿瘤和抑制作用。然而,控制 IL-6 对癌症进展结果的机制仍有待阐明。我们的研究揭示了一种位于 IL-6 信号通路下游的新型长链非编码 RNA (lncRNA) AU021063。我们发现与其他癌症类型相比,IL-6 主要在乳腺癌中诱导 AU021063 的表达。从机制上讲,IL-6 诱导了富含 AT 的交互结构域 5a (Arid5a) 表达,从而促进了 AU021063 的转录。反过来,AU021063 通过稳定 tribbles 同源物 3 (Trib3) 和激活 Mek/Erk 信号通路促进乳腺癌转移。Arid5a、AU021063 或 Trib3 的基因消融在体外体内消除了乳腺癌转移. 总体而言,我们的研究强调了 IL-6-Arid5a-AU021063 轴在调节乳腺癌侵袭和转移中的重要性,这可能为乳腺癌提供潜在的新疗法。

更新日期:2021-08-15
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