Genomic amplification of long noncoding RNA HOTAIRM1 drives anaplastic thyroid cancer progression via repressing miR-144 biogenesis
Ling Zhang, Jin Zhang, Shujing Li, Yanyan Zhang, Yun Liu, Jian Dong, Wenjun Zhao, Bo Yu, Huifang Wang, Jing Liu
Abstract
. HOTAIRM1 was found to bind ILF3, repress the binding between ILF3 and precursor miR-144 (pre-miR-144), block the effects of ILF3 on stabilizing pre-miR-144, and therefore downregulate pre-miR-144. Intriguingly, HOTAIRM1 was also found to directly bind primary miR-144 (pri-miR-144), repress the binding between pri-miR-144 and DROSHA, block the processing of pri-miR-144 by DROSHA, and therefore upregulate pri-miR-144 and downregulate pre-miR-144. Thus, HOTAIRM1 remarkably downregulated pre-miR-144 and further downregulated miR-144. Knockdown of ILF3 and DROSHA abolished the effects of HOTAIRM1 on pre-miR-144 and miR-144. The expression of miR-144 was downregulated and reversely correlated with HOTAIRM1 in ATC. Via repressing miR-144 biogenesis, HOTAIRM1 upregulated MET and activated AKT signalling. miR-144 overexpression reversed the oncogenic roles of HOTAIRM1 in ATC. Altogether, these findings identified a genomic copy number amplified and highly expressed lncRNA HOTAIRM1, which exerted oncogenic roles via repressing miR-144 biogenesis in ATC. Our data suggested HOTAIRM1 as a potential prognostic biomarker and therapeutic target for ATC.