长链非编码RNA（LncRNA）HOTAIR在肝癌的表观遗传调控以及癌变和发展过程中发挥重要作用。以往的研究表明HOTAIR的过表达预示着不良预后。本研究通过转录组测序数据和体外实验发现，在肝癌组织和细胞系中HOTAIR的表达更高，并且HOTAIR与NUAK1呈显著正相关。miR-145-5p的表达下调与HOTAIR和NUAK1呈负相关。通过转染Sh-HOTAIR、LZRS-HOTAIR、miR-145 mimic和miR-145 inhibitor来改变HOTAIR和miR-145-5p的表达。HTH-01-015的加入抑制了NUAK1的表达。HOTAIR的沉默、miR-145-5p的上调和NUAK1的抑制均抑制了SNU-387和HepG2细胞的迁移、侵袭和转移，并逆转了细胞上皮间质转化过程。我们还证明了HOTAIR通过与PRC2（EZH2）的结合来表观遗传地抑制miR-145-5p，而miR-145-5p调控了靶基因NUAK1，从而促进了肝癌细胞的上皮间质转化和肿瘤转移。此外，我们还证明了HOTAIR与miR-145-5p/NUAK1在表观遗传调控期间的相互作用。我们的研究结果表明，HOTAIR/miR-145-5p/NUAK1轴扮演了上皮间质转化调控因子的角色，并可能成为肝癌新疗法的候选预后生物标志物和靶标。© 作者。

LncRNA HOTAIR play important roles in the epigenetic regulation of carcinogenesis and progression in liver cancer. Previous studies suggest that the overexpression of HOTAIR predicts poor prognosis. In this study, through transcriptome sequencing data and in vitro experiments, we found that HOTAIR were more highly expressed and there is significantly positive relationship between HOTAIR and NUAK1 in liver cancer tissues and cell lines. miR-145-5p was downregulated and showed negative correlation with HOTAIR and NUAK1. Transfect Sh-HOTAIR, LZRS-HOTAIR, miR-145 mimic, miR-145 inhibitor to change the expression of HOTAIR and miR-145-5p. The addition of HTH-01-015 inhibits the expression of NUAK1. HOTAIR knockdown, miR-145-5p upregulation and NUAK1 inhibition all repressed migration, invasion and metastasis and reversed the epithelial-to-mesenchymal transition in SNU-387 and HepG2 cells. We also showed that HOTAIR recruiting and binding PRC2 (EZH2) epigenetically represses miR-145-5p, which controls the target NUAK1, thus contributing to liver cancer cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with miR-145-5p/NUAK1 during epigenetic regulation. Our findings indicate that HOTAIR/miR-145-5p/NUAK1 axis acts as an EMT regulator and may be candidate prognostic biomarker and targets for new therapies in liver cancer.© The author(s).