Research Paper Volume 16, Issue 8 pp 6868—6882
lincRNA00907 promotes NASH progression by targeting miRNA-942-5p/TAOK1
- 1 Organ Transplant Department, Qilu Hospital of Shangdong University, Jinan 250012, China
- 2 Department of Hepatobiliary Surgery, The Second Hospital of Shangdong University, Jinan 250033, China
Received: October 10, 2023 Accepted: February 27, 2024 Published: April 10, 2024
https://doi.org/10.18632/aging.205730How to Cite
Copyright: © 2024 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: The study aims to examine the involvement of lincRNA00907 in the advancement of non-alcoholic steatohepatitis (NASH).
Methods: The examination was conducted to assess the expression of linc00907 in liver tissues from NASH patients and healthy individuals. High-fat diets induced NASH in mouse models, while palmitic acid/oleic acid treatment was used to create in vitro cell models. Various techniques, such as qRT-PCR, Oil Red O staining and gene knockdown/overexpression, were used to assess the impact of linc00907 on genes related to lipid metabolism and immunity, as well as intracellular lipid accumulation. Furthermore, dual-luciferase reporter assays were carried out to confirm the connection between miRNA-942-5p and linc00907 or TAOK1 mRNA.
Results: Linc00907 was found to be significantly upregulated in both NASH patients and NASH mouse models. Overexpression of linc00907 led to an increase in intracellular lipid accumulation, while knockdown of linc00907 resulted in decreased lipid content. It was found that miRNA-942-5p binds with linc00907, and their interaction was confirmed in dual-luciferase reporter assays. Additionally, TAOK1 was predicted to be a downstream target of miRNA-942-5p, and the upregulation of TAOK1 due to linc00907 was reversed by miRNA-942-5p overexpression. linc00907 overexpression reduces apoptosis but can be reversed by TAOK1 knockdown. The reduction of TAOK1 counteracted the impact of linc00907 on gene expression associated with lipid metabolism and immunity, as well as on the accumulation of intracellular lipids.
Conclusions: Our research suggests that linc00907 functions as a competitive endogenous RNA (ceRNA) by sequestering miRNA-942-5p, thus increasing the expression of TAOK1 and encouraging lipid accumulation in hepatocytes, leading to the aggravation of NASH development. Targeting the linc00907/miRNA-942-5p/TAOK1 axis may hold therapeutic potential for the treatment of NASH.