非编码长链RNA（lncRNA）在肝细胞癌（HCC）的肿瘤进展中起着至关重要的作用。验证了lnc-ZEB2-19在HCC中的缺乏表达。然而，lnc-ZEB2-19的功能和潜在机制仍然不明确。在本研究中，我们验证了lnc-ZEB2-19的下调在HCC中普遍存在，并且与不良预后显著相关。进一步的体外和体内验证表明，lnc-ZEB2-19显著抑制了HCC细胞的增殖、转移、干细胞特性和雷伐替尼耐药性。在机制上，lnc-ZEB2-19通过特异性结合转换因子2α（TRA2A）并促进其降解，从而抑制HCC进展和雷伐替尼耐药性，导致RSPH14 mRNA的不稳定性，这导致Rela(p65)和p-Rela(p-p65)的下调。此外，救助实验表明，沉默RSPH14部分抑制了lnc-ZEB2-19的表达下调对HCC细胞转移能力和干细胞特性的影响。这些研究结果描述了一种新的调控轴，lnc-ZEB2-19 /TRA2A /RSPH14，通过下调核因子kappa B来抑制HCC进展和雷伐替尼耐药性。©作者。

Long non-coding RNAs have been reported to play a crucial role in tumor progression in hepatocellular carcinoma (HCC). Lnc-ZEB2-19 has been validated to be deficiently expressed in HCC. However, the capabilities and underlying mechanisms of lnc-ZEB2-19 remain uncertain. In this study, we verified that the downregulation of lnc-ZEB2-19 was prevalent in HCC and significantly correlated with the unfavorable prognosis. Further in vitro and in vivo verified that lnc-ZEB2-19 notably inhibited the proliferation, metastasis, stemness, and lenvatinib resistance (LR) of HCC cells. Mechanistically, lnc-ZEB2-19 inhibited HCC progression and LR by specifically binding to transformer 2α (TRA2A) and promoting its degradation, which resulted in the instability of RSPH14 mRNA, leading to the downregulation of Rela(p65) and p-Rela(p-p65). Furthermore, rescue assays showed that silencing RSPH14 partially restrained the effect of knockdown expression of lnc-ZEB2-19 on HCC cell metastatic ability and stemness. The findings describe a novel regulatory axis, lnc-ZEB2-19/TRA2A/RSPH14, downregulating the nuclear factor kappa B to inhibit HCC progression and LR.© The author(s).