The aggravating role of long noncoding RNA (lncRNA) HOTAIR has been indicated in liver injury caused by hepatic ischemia/reperfusion. However, under the condition of alcoholic hepatitis (AH), its effects remain unclear. The present study aimed to examine the effect of lncRNA HOTAIR on hepatic stellate cell viability and apoptosis during liver injury caused by AH. In the liver tissues of AH rats, HOTAIR and S1PR1 were overexpressed, and microRNA (miR)-148a-3p was poorly expressed. Loss-of-function assays revealed that silencing of HOTAIR alleviated liver injury in AH by inhibiting the activated phenotype of hepatic stellate cells, inflammation, and fibrosis. Using the bioinformatics databases, dual-luciferase, RIP, and FISH assays, we observed that HOTAIR was mainly localized in the cytoplasm of hepatic stellate cells, and HOTAIR could bind specifically to miR-148a-3p. In addition, miR-148a-3p could target S1PR1 expression. Rescue experiments showed that silencing of miR-148a-3p or overexpression of S1PR1 reversed the alleviating effects of HOTAIR silencing on liver injury. Taken together, our findings revealed that HOTAIR regulates hepatic stellate cell proliferation via the miR-148a-3p/S1PR1 axis in liver injury, which may serve as the basis for developing novel therapeutic strategies to treat AH.

长链非编码 RNA (lncRNA) HOTAIR 在肝缺血/再灌注引起的肝损伤中具有加重作用。然而，在酒精性肝炎（AH）的情况下，其作用仍不清楚。本研究旨在探讨 lncRNA HOTAIR 对 AH 引起的肝损伤期间肝星细胞活力和凋亡的影响。在AH大鼠的肝组织中，HOTAIR和S1PR1过表达，而microRNA（miR）-148a-3p表达较差。功能丧失检测显示，HOTAIR 的沉默通过抑制肝星状细胞的激活表型、炎症和纤维化来减轻 AH 中的肝损伤。利用生物信息学数据库、双荧光素酶、RIP和FISH检测，我们观察到HOTAIR主要定位于肝星状细胞的细胞质，并且HOTAIR可以与miR-148a-3p特异性结合。此外，miR-148a-3p 可以靶向 S1PR1 表达。拯救实验表明，沉默 miR-148a-3p 或过度表达 S1PR1 可逆转 HOTAIR 沉默对肝损伤的缓解作用。综上所述，我们的研究结果表明，HOTAIR 在肝损伤中通过 miR-148a-3p/S1PR1 轴调节肝星状细胞增殖，这可能作为开发治疗 AH 的新治疗策略的基础。