Hypermethylation reduces the expression of PNPLA7 in hepatocellular carcinoma

Zhang, Xiaojiao; Zhang, Jun; Wang, Rui; Guo, Shicheng; Zhang, Huilu; Ma, Yanyun; Liu, Qingmei; Chu, Haiyan; Xu, Xianghong; Zhang, Yitong; Yang, Dongqin; Wang, Jiucun; Liu, Jie

doi:10.3892/ol.2016.4660

Cited by 9 publications

(11 citation statements)

References 26 publications

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“…A previous study by Zhang et al also reported the down‐regulation of PNPLA7 levels in both hepatocellular carcinoma (HCC) cell lines and tissues. ( 37 ) In addition, the clinical data available in this current study are single‐point measurements. Patients with high PNPLA7 are diagnosed as less severe; thus, PNPLA7 expression may serve as a good prognostic marker for fatty liver, such that only patients with lower PNPLA7 expression progress just like HCC.…”

Section: Discussionmentioning

confidence: 99%

The Patatin‐Like Phospholipase Domain Containing Protein 7 Facilitates VLDL Secretion by Modulating ApoE Stability

et al. 2020

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Background and Aims The regulation of hepatic very‐low‐density lipoprotein (VLDL) secretion is vital for lipid metabolism whose pathogenetic status is involved in fatty liver disease and dyslipidemia seen in hepatic steatosis. Accumulated evidence suggest that apolipoprotein E (ApoE) is closely related to hepatic VLDL secretion. Here, we report that the expression of patatin‐like phospholipase domain containing protein 7 (PNPLA7) is strongly induced by hepatic steatosis and positively correlates with plasma triacylglycerol (TAG) levels in the human subjects, whereas the role of PNPLA7 in hepatic VLDL secretion is unknown. Approach and Results Herein, with genetic manipulation in the mice, the deficiency of hepatic PNPLA7 expression resulted in reduced VLDL secretion accompanied by enhanced hepatic lipid accumulation and decreased hepatic ApoE expression. Furthermore, knockdown of PNPLA7 in the livers of the db/db mice also resulted in significant reduction in plasma TAG level but aggravated hepatic steatosis. Importantly, we observed that PNPLA7 interacted with ApoE and presumably at the site of endoplasmic reticulum. Mechanistically, we have shown that PNPLA7 could modulate polyubiquitination and proteasomal‐mediated degradation of ApoE. Overexpressed ApoE restored the impaired VLDL‐TAG metabolism in PNPLA7‐knockdown primary hepatocytes. Conclusion PNPLA7 plays a critical role in regulating hepatic VLDL secretion by modulating ApoE stability through its interaction with ApoE.

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Section: Discussionmentioning

confidence: 99%

The Patatin‐Like Phospholipase Domain Containing Protein 7 Facilitates VLDL Secretion by Modulating ApoE Stability

et al. 2020

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“…PNPLA7 (also known as NTE-R1 or NRE ) is a member of the PNPLAs family, and its encoded protein is very conservative in mice, rats and human. PNPLA7 plays an important role in the hydrolysis of triglycerides, energy metabolism, lipid formation and adipocyte differentiation [ 20 ]. Up-regulation of PNPLA7 indicates elevated blood lipids, which has some correlation with hypertension.…”

Section: Discussionmentioning

confidence: 99%

Identification of differential gene expression profile from peripheral blood cells of military pilots with hypertension by RNA sequencing analysis

et al. 2018

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BackgroundElevated blood pressure is an important risk factor for cardiovascular disease and is also an important factor in global mortality. Military pilots are at high risk of cardiovascular disease because they undergo persistent noise, high mental tension, high altitude hypoxia, high acceleration and high calorie diet. Hypertension is the leading cause of cardiovascular disease in military pilots. In this study, we want to identify key genes from peripheral blood cells of military pilots with hypertension. Identification of these genes may help diagnose and control hypertension and extend flight career for military pilots.MethodsWe use RNA sequencing technology, bioinformatics analysis and Western blotting to identify key genes from peripheral blood cells of military pilots with hypertension.ResultsOur study detected 121 up-regulated genes and 623 down-regulated genes in the peripheral blood mononuclear cells (PBMCs) from hypertensive military pilots. We have also identified 8 important genes (NME4, PNPLA7, GGT5, PTGS2, IGF1R, NT5C2, ENTPD1 and PTEN), a number of gene ontology categories and biological pathways that may be associated with military pilot hypertension.ConclusionsOur study may provide effective means for the prevention, diagnosis and treatment of hypertension for military pilot and extend their flight career.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0378-2) contains supplementary material, which is available to authorized users.

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“…LPA is upregulated with adipocyte differentiation and obesity 46 and, therefore, it does not come as a surprise that PNPLA7 would be then less expressed in samples from obese pregnancies. In addition, it has also been reported that DNA methylation regulates PNPLA7 expression - it is down-regulated in hepatocellular carcinoma cell lines and tissue samples, via the mechanism of transcriptional silencing by promoter hypermethylation 47 .…”

Section: Discussionmentioning

confidence: 99%

Effects of maternal obesity on Wharton’s Jelly mesenchymal stromal cells

Badraiq

Čvoro

Galleu

et al. 2017

Sci Rep

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We investigated whether maternal metabolic environment affects mesenchymal stromal/stem cells (MSCs) from umbilical cord’s Wharton’s Jelly (WJ) on a molecular level, and potentially render them unsuitable for clinical use in multiple recipients. In this pilot study on umbilical cords post partum from healthy non-obese (BMI = 19–25; n = 7) and obese (BMI ≥ 30; n = 7) donors undergoing elective Cesarean section, we found that WJ MSC from obese donors showed slower population doubling and a stronger immunosuppressive activity. Genome-wide DNA methylation of triple positive (CD73+CD90+CD105+) WJ MSCs found 67 genes with at least one CpG site where the methylation difference was ≥0.2 in four or more obese donors. Only one gene, PNPLA7, demonstrated significant difference on methylome, transcriptome and protein level. Although the number of analysed donors is limited, our data suggest that the altered metabolic environment related to excessive body weight might bear consequences on the WJ MSCs.

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Hypermethylation reduces the expression of PNPLA7 in hepatocellular carcinoma

Cited by 9 publications

References 26 publications

The Patatin‐Like Phospholipase Domain Containing Protein 7 Facilitates VLDL Secretion by Modulating ApoE Stability

The Patatin‐Like Phospholipase Domain Containing Protein 7 Facilitates VLDL Secretion by Modulating ApoE Stability

Identification of differential gene expression profile from peripheral blood cells of military pilots with hypertension by RNA sequencing analysis

Effects of maternal obesity on Wharton’s Jelly mesenchymal stromal cells

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