The novel long noncoding RNA lncRNA-AU021063, induced by IL-6/Arid5a signaling, exacerbates breast cancer invasion and metastasis by stabilizing Trib3 and activating the Mek/Erk pathway (ncRNA-Seq)

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 lncRNA-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 lncRNA-AU021063. In turn, lncRNA-AU021063 promotes breast cancer metastasis through stabilizing tribbles homolog 3 (Trib3) and activating Mek/Erk signaling pathway. Genetic ablation of either Arid5a, lncRNA-AU021063 or Trib3 abolished breast cancer metastasis in vitro and in vivo. Overall, our study highlights the importance of IL-6-Arid5a-lncRNA-AU021063 axis in regulating breast cancer invasiveness and metastasis, which may provide potential novel therapeutics for breast cancer. To identify novel lncRNAs that may be involved in the pathogenesis of breast cancer associated with IL-6/Arid5a signaling, we performed next-generation RNA sequencing (lncRNA sequencing) in stimulated WT and Arid5a-/- MEFs with or without IL-6 treatment.