Mammalian genome : official journal of the International Mammalian Genome Society最新文献

{"title":"Mutation of the Thap4 gene causes dwarfism and testicular anomalies in rats and mice.","authors":"K. Katayama, Junya Ito, Rei Murakami, Ayako Yamashita, Hotaka Sasajima, Satomi Narahashi, J. Chiba, Ichiro Yamamoto, Wataru Fujii, Yuki Tochigi, Hiroetsu Suzuki","doi":"10.1007/s00335-024-10041-8","DOIUrl":"https://doi.org/10.1007/s00335-024-10041-8","url":null,"abstract":"","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":"63 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing circ_0074371 inhibits the progression of sepsis-induced acute kidney injury by regulating miR-330-5p/ELK1 axis.","authors":"Qiu-Yuan Wang,&nbsp;Rong-Rong Zhang,&nbsp;Long Cui,&nbsp;Ya-Ping Sun","doi":"10.1007/s00335-022-09961-0","DOIUrl":"https://doi.org/10.1007/s00335-022-09961-0","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced acute kidney injury (AKI) is a common in clinic. Circular RNAs (circRNAs) play significant roles in ameliorating AKI. The purpose of this study was aimed to identify the role of circ_0074371 and the potential action mechanism in sepsis-induced AKI.</p><p><strong>Methods: </strong>AKI patients and healthy individual serum samples were collected and the relative expression of circ_0074371 was measured by real-time polymerase chain reaction (RT-PCR). HK2 cells were treated with different dose (0, 2.5, 5 and 10 μg/ml) lipopolysaccharide (LPS) to establish the AKI cell model. The cell viability and apoptosis of HK2 cells were detected using cell counting kit-8 (CCK-8) and flow cytometry, respectively. The contents of malondialdehyde (MDA), and superoxide dismutase (SOD) were evaluated using the relative commercial kits. The IL-1β and TNF-α levels in cell culture supernatants were measured by ELISA. The interaction relationship between miR-330-5p and circ_0074371 or ELK1 was predicted by Targetscan database and further confirmed by the dual-luciferase reporter assay system.</p><p><strong>Results: </strong>The circ_0074371 expression was up-regulated in sepsis patients and LPS-induced HK2 cells. Silencing circ_0074371 promoted HK2 cells viability and inhibited the HK2 cells apoptosis. miR-330-5p inhibitor weakened circ_0074371 inhibitor-induced cell viability, apoptosis and oxidative stress. Further mechanism analysis showed that circ_0074371 acted as a sponge for miR-330-5p to increase ELK1 expression level. Importantly, miR-330-5p downregulation or ELK1 upregulation reversed the action of circ_0074371 knockdown on LPS-induced HK2 cells.</p><p><strong>Conclusion: </strong>Knockdown of circ_0074371 ameliorated LPS-induced HK2 cells apoptosis, inflammation and oxidative stress via regulating miR-330-5p/ELK1, opening a new window into the pathogenesis AKI.</p>","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":" ","pages":"642-653"},"PeriodicalIF":2.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40434280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WTAP mediates FOXP3 mRNA stability to promote SMARCE1 expression and augment glycolysis in colon adenocarcinoma.","authors":"Yu Zhang,&nbsp;Xiaoxiao Tian,&nbsp;Yanli Bai,&nbsp;Xianmin Liu,&nbsp;Jingjing Zhu,&nbsp;Lamei Zhang,&nbsp;Jinliang Wang","doi":"10.1007/s00335-022-09962-z","DOIUrl":"https://doi.org/10.1007/s00335-022-09962-z","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) is the most abundant mRNA internal modification and has reportedly been linked to aerobic glycolysis, a hallmark event in tumor development. This work focuses on the role of the m6A methyltransferase WT1-associated protein (WTAP) in metabolic reprogramming and development of colon adenocarcinoma (COAD) and the molecules involved. The WTAP expression in COAD tissues and cells was detected. WTAP was knocked down in two COAD cell lines to figure out its role in the glycolytic activity and malignant phenotype of cancer cells. Cancer cells were further injected into nude mice subcutaneously or via tail vein to evaluate tumor growth and metastasis. The downstream molecules involved were explored using bioinformatics tools, and the molecular interactions were confirmed by immunoprecipitation, luciferase assays, and rescue experiments. WTAP was abundantly expressed in COAD samples. Knockdown of WTAP suppressed glucose consumption, lactate production, and glycolysis, which consequently suppressed cancer cell growth and dissemination in vitro and in vivo. WTAP promoted m6A methylation and stabilized forkhead box P3 (FOXP3) mRNA with the participation of the m6A \"reader\" YTHDF1. FOXP3 could further bind to SMARCE1 promoter for transcriptional activation. Rescue experiments showed that upregulation of FOXP3 or SMARCE1 restored the glycolytic activity in COAD cells and augmented the growth and mobility of cells both in vitro and in vivo. This study demonstrates that WTAP grants glycolytic activity to COAD and promotes tumor malignant development via the m6A modification of FOXP3 mRNA and the upregulation of SMARCE1.</p>","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":" ","pages":"654-671"},"PeriodicalIF":2.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40381939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prune homolog 2 with BCH domain (PRUNE2) gene expression is associated with feed efficiency-related traits in Nelore steers.","authors":"Andressa Oliveira Lima,&nbsp;Jessica Moraes Malheiros,&nbsp;Juliana Afonso,&nbsp;Juliana Petrini,&nbsp;Luiz Lehmann Coutinho,&nbsp;Wellison Jarles da Silva Diniz,&nbsp;Flávia Aline Bressani,&nbsp;Polyana Cristine Tizioto,&nbsp;Priscila Silva Neubern de Oliveira,&nbsp;Janssen Ayna Silva Ribeiro,&nbsp;Karina Santos de Oliveira,&nbsp;Marina Ibelli Pereira Rocha,&nbsp;Bruno Gabriel Nascimento Andrade,&nbsp;Heidge Fukumasu,&nbsp;Hamid Beiki,&nbsp;James Mark Reecy,&nbsp;Adhemar Zerlotini,&nbsp;Gerson Barreto Mourao,&nbsp;Luciana Correia de Almeida Regitano","doi":"10.1007/s00335-022-09960-1","DOIUrl":"https://doi.org/10.1007/s00335-022-09960-1","url":null,"abstract":"<p><p>Animal feeding is a critical factor in increasing producer profitability. Improving feed efficiency can help reduce feeding costs and reduce the environmental impact of beef production. Candidate genes previously identified for this trait in differential gene expression studies (e.g., case-control studies) have not examined continuous gene-phenotype variation, which is a limitation. The aim of this study was to investigate the association between the expression of five candidate genes in the liver, measured by quantitative real-time PCR and feed-related traits. We adopted a linear mixed model to associate liver gene expression from 52 Nelore steers with the following production traits: average daily gain (ADG), body weight (BW), dry matter intake (DMI), feed conversion ratio (FCR), feed efficiency (FE), Kleiber index (KI), metabolic body weight (MBW), residual feed intake (RFI), and relative growth ratio (RGR). The total expression of the prune homolog 2 (PRUNE2) gene was significantly associated with DMI, FCR, FE, and RFI (P &lt; 0.05). Furthermore, we have identified a new transcript of PRUNE2 (TCONS_00027692, GenBank MZ041267) that was inversely correlated with FCR and FE (P &lt; 0.05), in contrast to the originally identified PRUNE2 transcript. The cytochrome P450 subfamily 2B (CYP2B6), early growth response protein 1 (EGR1), collagen type I alpha 1 chain (COL1A1), and connective tissue growth factor (CTGF) genes were not associated with any feed efficiency-related traits (P &gt; 0.05). The findings reported herein suggest that PRUNE2 expression levels affects feed efficiency-related traits variation in Nelore steers.</p>","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":" ","pages":"629-641"},"PeriodicalIF":2.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40607539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-associated changes in gene expression in the anterior pituitary glands of female Japanese black cattle.","authors":"Dimas Arya Abdillah,&nbsp;Onalenna Kereilwe,&nbsp;Yoichi Mizukami,&nbsp;Kenji Watanabe,&nbsp;Hiroya Kadokawa","doi":"10.1007/s00335-022-09958-9","DOIUrl":"https://doi.org/10.1007/s00335-022-09958-9","url":null,"abstract":"<p><p>Proper functioning of the anterior pituitary (AP) gland is imperative, however, is suppressed by aging via unclear mechanisms. Therefore, we identified differentially expressed genes (DEGs) in the AP glands of Japanese Black young heifers (approximately 22 months old) compared to old cows (approximately 120 months old) via deep sequencing of the transcriptome (RNA-seq) to characterize potentially important pathways. The young and old AP glands expressed 20,171 annotated genes. Of the total transcripts per million, approximately 41.6% and 35.5% were the sum of seven AP hormone genes in young and old AP glands, respectively, with difference observed in the sum between the young and old AP glands (P &lt; 0.05). Moreover, we identified 48 downregulated genes and 218 upregulated genes in old compared to young AP glands (P &lt; 0.01, fold change &gt; 120%). The DEGs included 1 cytokine (AIMP1), 3 growth factors (NRG2, PTN, and TGFB1), 1 receptor-associated protein gene (AGTRAP), and 10 receptor genes, including PRLHR and two orphan G-protein-coupled receptors (GPR156 and GPR176). Metascape analysis of the DEGs revealed \"Peptide metabolic process,\" \"Regulation of hormone levels,\" and \"Peptide hormone processing\" as enriched pathways. Furthermore, Ingenuity Pathway analysis of the DEGs revealed (1) a network of 24 genes (including GPR156 and PRLHR) named \"Neurological disease, organismal injury and abnormalities, and psychological disorders\", and (2) two canonical pathways (P &lt; 0.01), namely \"Huntington's disease signaling\", and \"AMPK signaling\". Thus, the findings of the current study revealed relevant DEGs, while identifying important pathways that occur during aging in AP glands of female cattle.</p>","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":" ","pages":"606-618"},"PeriodicalIF":2.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40595891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EEF1A1 transcription cofactor gene polymorphism is associated with muscle gene expression and residual feed intake in Nelore cattle.","authors":"T F Cardoso,&nbsp;J J Bruscadin,&nbsp;J Afonso,&nbsp;J Petrini,&nbsp;B G N Andrade,&nbsp;P S N de Oliveira,&nbsp;J M Malheiros,&nbsp;M I P Rocha,&nbsp;A Zerlotini,&nbsp;J B S Ferraz,&nbsp;G B Mourão,&nbsp;L L Coutinho,&nbsp;L C A Regitano","doi":"10.1007/s00335-022-09959-8","DOIUrl":"https://doi.org/10.1007/s00335-022-09959-8","url":null,"abstract":"<p><p>Cis-acting effects of noncoding variants on gene expression and regulatory molecules constitute a significant factor for phenotypic variation in complex traits. To provide new insights into the impacts of single-nucleotide polymorphisms (SNPs) on transcription factors (TFs) and transcription cofactors (TcoF) coding genes, we carried out a multi-omic analysis to identify cis-regulatory effects of SNPs on these genes' expression in muscle and describe their association with feed efficiency-related traits in Nelore cattle. As a result, we identified one SNP, the rs137256008C &gt; T, predicted to impact the EEF1A1 gene expression (β = 3.02; P-value = 3.51E-03) and the residual feed intake trait (β = - 3.47; P-value = 0.02). This SNP was predicted to modify transcription factor sites and overlaps with several QTL for feed efficiency traits. In addition, co-expression network analyses showed that animals containing the T allele of the rs137256008 SNP may be triggering changes in the gene network. Therefore, our analyses reinforce and contribute to a better understanding of the biological mechanisms underlying gene expression control of feed efficiency traits in bovines. The cis-regulatory SNP can be used as biomarker for feed efficiency in Nelore cattle.</p>","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":" ","pages":"619-628"},"PeriodicalIF":2.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40580812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of lncRNA MIAT attenuated lipopolysaccharide-induced microglial cells injury by sponging miR-613.","authors":"Jia Li,&nbsp;Chang-Lin Zou,&nbsp;Zhi-Ming Zhang,&nbsp;Feng Xue","doi":"10.1007/s00335-022-09946-z","DOIUrl":"https://doi.org/10.1007/s00335-022-09946-z","url":null,"abstract":"<p><p>Microglia activation and its mediated neuroinflammation play an important role in the pathological process of various central nervous system injuries and diseases. Previous studies have reported abnormal expression of lncRNAs participated in neuroinflammation. However, the expression pattern and involvements of MIAT in neuroinflammatory diseases are not fully investigated. We first screened abnormal expressed lncRNAs in BV2 cells treated with LPS. The expression of MIAT in LPS-induced BV2 cells was detected by qRT-PCR. MTT assay, cell migration, flow cytometry analysis, ELISA, qRT-PCR, and Western blotting analysis were applied to evaluating the effect of si-MIAT on LPS-induced H9C2 cells. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism of lncRNA-miRNA-mRNA network. The results showed LncRNA MIAT expression was significantly increased in LPS-induced BV2 microglial cells. Besides, MIAT knockdown alleviated LPS-induced repression of cell viability and induction of apoptosis and inflammatory response in BV2 cells. Furthermore, LncRNA MIAT regulated NFAT5 expression via sponging miR-613 in LPS-induced BV2 cells. Altogether, these results suggest that lncRNA MIAT functioned as a ceRNA for miR-613 to modulate NFAT5 expression in LPS-induced BV2 cells, which may contribute to a better understanding of the mechanism of neuroinflammatory diseases.</p>","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":" ","pages":"471-479"},"PeriodicalIF":2.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39859710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of murine type 2 diabetes and comorbidities.","authors":"Iqbal M Lone,&nbsp;Fuad A Iraqi","doi":"10.1007/s00335-022-09948-x","DOIUrl":"https://doi.org/10.1007/s00335-022-09948-x","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is a polygenic and multifactorial complex disease, defined as chronic metabolic disorder. It's a major global health concern with an estimated 463 million adults aged 20-79 years with diabetes and projected to increase up to 700 million by 2045. T2D was reported to be one of the four leading causes of non-communicable disease (NCD) deaths in 2012. Environmental factors play a part in the development of polygenic forms of diabetes. Polygenic forms of diabetes often run-in families. Fortunately, T2D, which accounts for 90-95% of the entire four types of diabetes including, Type 1 diabetes (T1D), T2D, monogenic diabetes syndromes (MGDS), and Gestational diabetes mellitus, can be prevented or delayed through nutrition and lifestyle changes as well as through pharmacologic interventions. Typical symptom of the T2D is high blood glucose levels and comprehensive insulin resistance of the body, producing an impaired glucose tolerance. Impaired glucose tolerance of T2D is accompanied by extensive health complications, including cardiovascular diseases (CVD) that vary in morbidity and mortality among populations. The pathogenesis of T2D varies between populations and/or ethnic groupings and is known to be attributed extremely by genetic components and environmental factors. It is evident that genetic background plays a critical role in determining the host response toward certain environmental conditions, whether or not of developing T2D (susceptibility versus resistant). T2D is considered as a silent disease that can progress for years before its diagnosis. Once T2D is diagnosed, many metabolic malfunctions are observed whether as side effects or as independent comorbidity. Mouse models have been proven to be a powerful tool for mapping genetic factors that underline the susceptibility to T2D development as well its comorbidities. Here, we have conducted a comprehensive search throughout the published data covering the time span from early 1990s till the time of writing this review, for already reported quantitative trait locus (QTL) associated with murine T2D and comorbidities in different mouse models, which contain different genetic backgrounds. Our search has resulted in finding 54 QTLs associated with T2D in addition to 72 QTLs associated with comorbidities associated with the disease. We summarized the genomic locations of these mapped QTLs in graphical formats, so as to show the overlapping positions between of these mapped QTLs, which may suggest that some of these QTLs could be underlined by sharing gene/s. Finally, we reviewed and addressed published reports that show the success of translation of the identified mouse QTLs/genes associated with the disease in humans.</p>","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":" ","pages":"421-436"},"PeriodicalIF":2.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39760993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of gene polymorphisms in MYH11 and TGF-β signaling with the susceptibility and clinical outcomes of DeBakey type III aortic dissection.","authors":"Yafei Chang,&nbsp;Qinghua Yuan,&nbsp;Peipei Jiang,&nbsp;Ling Sun,&nbsp;Yitong Ma,&nbsp;Xiang Ma","doi":"10.1007/s00335-021-09929-6","DOIUrl":"https://doi.org/10.1007/s00335-021-09929-6","url":null,"abstract":"<p><p>To investigate the association of myosin heavy chain protein 11 (MYH11) and transforming growth factor β signaling-related gene polymorphisms with the susceptibility of DeBakey type III aortic dissection (AD) and its clinical outcomes. Four single-nucleotide polymorphism (SNPs) (MYH11 rs115364997, rs117593370, TGFB1 rs1800469, and TGFBR1 rs1626340) were analyzed in patients with DeBakey III AD (173) and healthy participants (335). Gene-gene and gene-environment interactions were evaluated using generalized multifactor dimensionality reduction. The patients were followed up for a median of 55.7 months. MYH11 rs115364997 G or TGFBR1 rs1626340 A carriers had an increased risk of DeBakey type III AD. MYH11, TGFB1, TGFBR1, and environment interactions contributed to the risk of DeBakey type III AD (cross-validation consistency = 10/10, P = 0.001). Dominant models of MYH11 rs115364997 AG + GG genotype (HR = 2.443; 95%CI: 1.096-5.445, P = 0.029), TGFB1 rs1800469 AG + GG (HR = 2.303; 95%CI: 1.069-4.96, P = 0.033) were associated with an increased risk of mortality in DeBakey type III AD. The dominant model of TGFB1 rs1800469 AG + GG genotype was associated with an increased risk of recurrence of chest pain in DeBakey type III AD (HR = 1.566; 95%CI: 1.018-2.378, P = 0.041). In conclusions, G carriers of MYH11 rs115364997 or TGFB1 rs1800469 may be the poor prognostic indicators of mortality and recurrent chest pain in DeBakey type III AD. The interactions of gene-gene and gene-environment are associated with the risk of DeBakey type III AD.</p>","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":" ","pages":"555-563"},"PeriodicalIF":2.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39585599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RMRP inhibition prevents NAFLD progression in rats via regulating miR-206/PTPN1 axis.","authors":"Jingjing Yin,&nbsp;Xiangfei Chen,&nbsp;Fang Zhang,&nbsp;Ming Zhao","doi":"10.1007/s00335-022-09945-0","DOIUrl":"https://doi.org/10.1007/s00335-022-09945-0","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":412165,"journal":{"name":"Mammalian genome : official journal of the International Mammalian Genome Society","volume":" ","pages":"480-489"},"PeriodicalIF":2.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39905593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}