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RMRP inhibition prevents NAFLD progression in rats via regulating miR-206/PTPN1 axis

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Abstract

This study aimed to investigate the regulatory function of lncRNA RMRP in non-alcoholic fatty liver disease (NAFLD). In vitro and in vivo NAFLD models were constructed. Hematoxylin & Eosin (H&E) and Oil-Red O staining assays were conducted to observe the morphology and lipid accumulation in liver tissues. Triglycine (TG) secretion was detected by ELISA assay. The expression levels of RMRP, microRNA-206, PTPN1 (protein tyrosine phosphatase, non-receptor type 1), and their downstream genes were assessed by qRT-PCR and Western blot. The regulatory relationship among these molecules was determined by luciferase reporter and RNA pull-down assays. RMRP and PTPN1 were up-regulated, while miR-206 was down-regulated in the liver tissues of NAFLD patients and rat model. RMRP inhibition improved the pathological state and liver function-related indexes of liver lipid deposition in the liver tissues of NAFLD rats. RMRP inhibition alleviated steatosis and TG secretion in free fatty acids (FFA)-treated AML-12 cells. RMRP could bind to miR-206 and downregulate its expression. Meanwhile, RMRP inhibition attenuated lipid accumulation by downregulating the PTPN1-PP2ASP1-SREBP1C pathway. Furthermore, RMRP inhibited the miR-206/PTPN1-SREBP1C signaling pathway in NAFLD rats and FFA-treated AML-12 cells. RMRP inhibition prevented NAFLD progression in rats via targeting the miR-206/PTPN1 axis.

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The datasets generated and/or analyzed during the current study are not publicly available due research design but are available from the corresponding author on reasonable request.

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Authors

Contributions

MZ and JJY: study concepts, study design, literature research, experimental studies, manuscript preparation and editing; XFC and FZ: definition of intellectual content, literature research experimental studies, manuscript preparation and editing; all authors read and approved the final manuscript.

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Correspondence to Ming Zhao.

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All the authors have declared that in the research there was no potential conflict of interest.

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This study was approved by the Ethics Committee of Jinling Hospital and carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans.

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Yin, J., Chen, X., Zhang, F. et al. RMRP inhibition prevents NAFLD progression in rats via regulating miR-206/PTPN1 axis. Mamm Genome 33, 480–489 (2022). https://doi.org/10.1007/s00335-022-09945-0

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  • DOI: https://doi.org/10.1007/s00335-022-09945-0

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