Palmitoylation of MDH2 by ZDHHC18 activates mitochondrial respiration and accelerates ovarian cancer growth

Pei, Xuan; Li, Kai-Yue; Yuan, Shuiqiao; Li, Jintao; Liu, Ming; Fang, Caiyun; Lu, Haojie; Yang, Huijuan; Wen, Wenyu; Yin, Miao; Qu, Jia; Lei, Qun‐Ying

doi:10.1007/s11427-021-2048-2

Cited by 33 publications

(21 citation statements)

References 60 publications

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“…Notably, ptgs2 participates in oocyte maturation, ovulation, and the regulation of apoptotic processes ( Park et al, 2021 ; Smith et al, 2022 ). Mdh2 regulates mitochondrial respiration and proliferation of ovarian cells ( Pei et al, 2022 ). In the KEGG-mRNA network, the analysis was mostly focused on the mTOR pathway.…”

Section: Discussionmentioning

confidence: 99%

Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats

Zhu

et al. 2022

Front. Genet.

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Acupuncture is widely used to improve ovarian function. Previously, we demonstrated that acupuncture can improve oxidative stress in rats with tripterygium glycoside tablet suspension (TG)-induced diminished ovarian reserve (DOR). Herein, we aimed to explore the antioxidation mechanism of acupuncture for ameliorating the ovarian reserve in DOR rats. We performed microRNA sequencing and bioinformatics analysis to screen differentially expressed miRNAs (DE miRNAs) in ovarian tissues. In total, 1,172 miRNAs were identified by miRNA sequencing, of which 28 DE miRNAs were detected (including 14 upregulated and 14 downregulated) in ovarian tissues from the acupuncture group when compared with the DOR model rats. Based on functional enrichment analysis, the target genes of DE miRNAs were significantly enriched in GO-biological process (BP) terms associated with biological processes, positive regulation of transcription by RNA polymerase II, signal transduction, regulation of transcription, DNA-templated processes, and oxidation–reduction processes. In the Kyoto Encyclopedia of Genes and Genomes analysis, the main pathways were the MAPK signaling pathway, hepatitis B, proteoglycans in cancer, human cytomegalovirus infection, and the Ras signaling pathway. Finally, reverse transcription-quantitative PCR results confirmed that rno-miR-92b-3p, mdo-miR-26b-5p_R+1_1ss10TC, and bta-miR-7857-3p_R-1 were downregulated in the acupuncture group. The results revealed the impact of acupuncture on miRNA profiling of ovarian tissues from DOR rats, suggesting that rno-miR-92b-3p, mdo-miR-26b-5p_R+1_1ss10TC, and bta-miR-7857-3p_R-1 might provide relevant cues to relieve DOR-mediated oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats

Zhu

et al. 2022

Front. Genet.

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“…Since the expression levels of palmitoylation regulators were aberrant in many cancer types and some palmitoylation regulators were closely associated with tumor development, we next explored whether the abnormal expression of the palmitoylation regulators was related to patient survival. Pei et al found that a higher level of ZDHHC18 mRNA expression was associated with poorer survival in patients with ovarian cancer and malate dehydrogenase 2 (MDH2) palmitoylation, catalyzed by ZDHHC18 , promoted the malignant progression of ovarian cancer [ 59 ]. BRCA patients with increased ZDHHC22 expressions were correlated with better relapse-free survival and ZDHHC22 suppressed proliferation by restraining the AKT/mTOR signaling pathway [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Dynamic Expression of Palmitoylation Regulators across Human Organ Development and Cancers Based on Bioinformatics

Jia

Long

Yang

2022

CIMB

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Protein palmitoylation is a reversible modification process that links palmitate to cysteine residues via a reversible thioester bond. Palmitoylation exerts an important role in human organ development and tumor progression. However, a comprehensive landscape regarding the dynamic expression of palmitoylation regulators in human organ development remains unclear. In this study, we analyzed the dynamic expression of palmitoylation regulators in seven organ development and eight cancer types based on bioinformatics. We found that the expression levels of most palmitoylation regulators were altered after birth. In particular, ZDHHC7/20/21 exhibited converse expression patterns in multiple cancer types. Survival analysis showed that the poor prognosis in patients with kidney renal clear carcinoma (KIRC) is related to low expression of ZDHHC7/20/21, and a high expression of ZDHHC7/20/21 is related to worse survival in patients with liver hepatocellular carcinoma (LIHC). Furthermore, we found that the expression of ZDHHC7 is associated with infiltration levels of some types of immune cells in the tumor microenvironment (TME), and we explored the relationship between ZDHHC7 expression and immune checkpoint (ICP) genes across 33 cancer types. In addition, gene set enrichment analysis (GSEA) results indicated that ZDHHC7 might regulate different genes to mediate the same pathway in different organs. In summary, the comprehensive analysis of palmitoylation regulators reveals their functions in human organ development and cancer, which may provide new insights for developing new tumor markers.

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“… 94 Due to its hydrophobic nature, the palmitoyl chain enhances the affinity between modified proteins and lipid membranes. 95 TMPRSS2, the viral entry priming protease, is at least in part regulated by palmitoylation 96 (Figure 2 ). Increased lipid levels in obese patients may result in TMPRSS2 hyper‐palmitoylation and enhance its membrane localization, explaining the SARS‐CoV‐2 vulnerability in overweight individuals.…”

Section: Host Metabolism Modulates Sars‐cov‐2 Lifecyclementioning

confidence: 99%

“…Fatty acylation is a PTM process during which fatty acids, such as palmitate, are attached to cysteine, serine, or threonine residues of proteins 94 . Due to its hydrophobic nature, the palmitoyl chain enhances the affinity between modified proteins and lipid membranes 95 . TMPRSS2, the viral entry priming protease, is at least in part regulated by palmitoylation 96 (Figure 2).…”

Section: Host Metabolism Modulates Sars‐cov‐2 Lifecyclementioning

confidence: 99%

COVID‐19 metabolism: Mechanisms and therapeutic targets

Wang

Cao

Zhang³

et al. 2022

MedComm

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) dysregulates antiviral signaling, immune response, and cell metabolism in human body. Viral genome and proteins hijack host metabolic network to support viral biogenesis and propagation. However, the regulatory mechanism of SARS‐CoV‐2‐induced metabolic dysfunction has not been elucidated until recently. Multiomic studies of coronavirus disease 2019 (COVID‐19) revealed an intensive interaction between host metabolic regulators and viral proteins. SARS‐CoV‐2 deregulated cellular metabolism in blood, intestine, liver, pancreas, fat, and immune cells. Host metabolism supported almost every stage of viral lifecycle. Strikingly, viral proteins were found to interact with metabolic enzymes in different cellular compartments. Biochemical and genetic assays also identified key regulatory nodes and metabolic dependencies of viral replication. Of note, cholesterol metabolism, lipid metabolism, and glucose metabolism are broadly involved in viral lifecycle. Here, we summarized the current understanding of the hallmarks of COVID‐19 metabolism. SARS‐CoV‐2 infection remodels host cell metabolism, which in turn modulates viral biogenesis and replication. Remodeling of host metabolism creates metabolic vulnerability of SARS‐CoV‐2 replication, which could be explored to uncover new therapeutic targets. The efficacy of metabolic inhibitors against COVID‐19 is under investigation in several clinical trials. Ultimately, the knowledge of SARS‐CoV‐2‐induced metabolic reprogramming would accelerate drug repurposing or screening to combat the COVID‐19 pandemic.

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Palmitoylation of MDH2 by ZDHHC18 activates mitochondrial respiration and accelerates ovarian cancer growth

Cited by 33 publications

References 60 publications

Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats

Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats

Dynamic Expression of Palmitoylation Regulators across Human Organ Development and Cancers Based on Bioinformatics

COVID‐19 metabolism: Mechanisms and therapeutic targets

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