Abstract
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.
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The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
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DC and PL: Conceptualization, Data curation, Experimental studies, Visualization, Software, Statistical analysis; TFS and ALD: Methodology, Experimental studies, Statistical analysis; Manuscript preparation, Reviewing and Editing, Validation; All authors read and approved the final manuscript.
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Chen, D., Lu, P., Sun, T. et al. Long non-coding RNA HOX transcript antisense intergenic RNA depletion protects against alcoholic hepatitis through the microRNA-148a-3p/sphingosine 1-phosphate receptor 1 axis. Cell Tissue Res 394, 471–485 (2023). https://doi.org/10.1007/s00441-023-03835-w
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DOI: https://doi.org/10.1007/s00441-023-03835-w