Demethylation of miR-34a upregulates expression of membrane palmitoylated proteins and promotes the apoptosis of liver cancer cells

Li, Fu-Yong; Fan, Tingyong; Zhang, Hao; Yuan, Sun

doi:10.3748/wjg.v27.i6.470

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…At present, the role and mechanism of MPP2 in cancer are rarely reported. In the only two in vitro studies on MPP2, Li et al (2021) confirmed that MPP2 can be up-regulated through miR-34a demethylation, promoted liver cancer cell apoptosis, and reduced proliferation, migration, and invasion. Similarly, Maschietto et alreported that the MPP2 gene was downregulated in relapse Wilms tumors ( Maschietto et al, 2011 ).…”

Section: Discussionmentioning

confidence: 90%

Identification of hub genes related to CD4+ memory T cell infiltration with gene co-expression network predicts prognosis and immunotherapy effect in colon adenocarcinoma

Tang

Yu²,

Zhang³

et al. 2022

Front. Genet.

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Background: CD4+ memory T cells (CD4+ MTCs), as an important part of the microenvironment affecting tumorigenesis and progression, have rarely been systematically analyzed. Our purpose was to comprehensively analyze the effect of CD4+ MTC infiltration on the prognosis of colon adenocarcinoma (COAD).Methods: Based on RNA-Seq data, weighted gene co-expression network analysis (WGCNA) was used to screen the CD4+ MTC infiltration genes most associated with colon cancer and then identify hub genes and construct a prognostic model using the least absolute shrinkage and selection operator algorithm (LASSO). Finally, survival analysis, immune efficacy analysis, and drug sensitivity analysis were performed to evaluate the role of the prognostic model in COAD.Results: We identified 929 differentially expressed genes (DEGs) associated with CD4+ MTCs and constructed a prognosis model based on five hub genes (F2RL2, TGFB2, DTNA, S1PR5, and MPP2) to predict overall survival (OS) in COAD. Kaplan–Meier analysis showed poor prognosis in the high-risk group, and the analysis of the hub gene showed that overexpression of TGFB2, DTNA, S1PR5, or MPP2 was associated with poor prognosis. Clinical prediction nomograms combining CD4+ MTC-related DEGs and clinical features were constructed to accurately predict OS and had high clinical application value. Immune efficacy and drug sensitivity analysis provide new insights for individualized treatment.Conclusion: We constructed a prognostic risk model to predict OS in COAD and analyzed the effects of risk score on immunotherapy efficacy or drug sensitivity. These studies have important clinical significance for individualized targeted therapy and prognosis.

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Section: Discussionmentioning

confidence: 90%

Identification of hub genes related to CD4+ memory T cell infiltration with gene co-expression network predicts prognosis and immunotherapy effect in colon adenocarcinoma

Tang

Yu²,

Zhang³

et al. 2022

Front. Genet.

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“…The upregulation of SCARA3 during disease progression from diagnosis to recurrence suggests that it plays a role in ovarian cancer biology [ 19 ]. The overexpression level of MPP2 in liver cancer cells promotes their apoptosis [ 20 ], and Huang C. reported that MPP2 is related to the 5-year survival rate of colon cancer patients [ 21 ]. A recent study revealed that PBXIP1 is a novel protein overexpressed in astrocytoma and ependymoma that is involved in tumour cell proliferation and migration and warrants further exploration as a novel therapeutic target in these tumours [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Single-cell and WGCNA uncover a prognostic model and potential oncogenes in colorectal cancer

Zhou

et al. 2022

Biol Proced Online

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Background Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Single-cell transcriptome sequencing (scRNA-seq) can provide accurate gene expression data for individual cells. In this study, a new prognostic model was constructed by scRNA-seq and bulk transcriptome sequencing (bulk RNA-seq) data of CRC samples to develop a new understanding of CRC. Methods CRC scRNA-seq data were downloaded from the GSE161277 database, and CRC bulk RNA-seq data were downloaded from the TCGA and GSE17537 databases. The cells were clustered by the FindNeighbors and FindClusters functions in scRNA-seq data. CIBERSORTx was applied to detect the abundance of cell clusters in the bulk RNA-seq expression matrix. WGCNA was performed with the expression profiles to construct the gene coexpression networks of TCGA-CRC. Next, we used a tenfold cross test to construct the model and a nomogram to assess the independence of the model for clinical application. Finally, we examined the expression of the unreported model genes by qPCR and immunohistochemistry. A clone formation assay and orthotopic colorectal tumour model were applied to detect the regulatory roles of unreported model genes. Results A total of 43,851 cells were included after quality control, and 20 cell clusters were classified by the FindCluster () function. We found that the abundances of C1, C2, C4, C5, C15, C16 and C19 were high and the abundances of C7, C10, C11, C13, C14 and C17 were low in CRC tumour tissues. Meanwhile, the results of survival analysis showed that high abundances of C4, C11 and C13 and low abundances of C5 and C14 were associated with better survival. The WGCNA results showed that the red module was most related to the tumour and the C14 cluster, which contains 615 genes. Lasso Cox regression analysis revealed 8 genes (PBXIP1, MPMZ, SCARA3, INA, ILK, MPP2, L1CAM and FLNA), which were chosen to construct a risk model. In the model, the risk score features had the greatest impact on survival prediction, indicating that the 8-gene risk model can better predict prognosis. qPCR and immunohistochemistry analysis showed that the expression levels of MPZ, SCARA3, MPP2 and PBXIP1 were high in CRC tissues. The functional experiment results indicated that MPZ, SCARA3, MPP2 and PBXIP1 could promote the colony formation ability of CRC cells in vitro and tumorigenicity in vivo. Conclusions We constructed a risk model to predict the prognosis of CRC patients based on scRNA-seq and bulk RNA-seq data, which could be used for clinical application. We also identified 4 previously unreported model genes (MPZ, SCARA3, MPP2 and PBXIP1) as novel oncogenes in CRC. These results suggest that this model could potentially be used to evaluate the prognostic risk and provide potential therapeutic targets for CRC patients.

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“…MPP2 is a type of membrane-associated protein belonging to a family of membrane-associated guanylate kinase homologs (MAGUKs). This protein has been demonstrated to be involved in a variety of cellular processes, such as promotion of tight junction formation, polarization of epithelial cells, and apoptosis of hepatocellular carcinoma cells [54,55]. In addition, this gene was found to act as an exon-specific accessory factor for ribosomal RNA maturation, which affects protein synthesis and controls cell growth by increasing the level of E7 protein [55][56][57].…”

Section: Discussionmentioning

confidence: 99%

A de novo missense mutation in MPP2 confers an increased risk of Vogt–Koyanagi–Harada disease as shown by trio-based whole-exome sequencing

Liu,

Meng,

Liao

et al. 2023

Cell Mol Immunol

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Vogt–Koyanagi–Harada (VKH) disease is a leading cause of blindness in young and middle-aged people. However, the etiology of VKH disease remains unclear. Here, we performed the first trio-based whole-exome sequencing study, which enrolled 25 VKH patients and 50 controls, followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations. A total of 15 de novo mutations in VKH patients were identified, with one of the most important being the membrane palmitoylated protein 2 (MPP2) p.K315N (MPP2-N315) mutation. The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions. Additionally, this mutation appears rare, being absent from the 1000 Genome Project and Genome Aggregation Database, and it is highly conserved in 10 species, including humans and mice. Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis (EAU). In vitro, we used clustered regularly interspaced short palindromic repeats (CRISPR‒Cas9) gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315. Levels of cytokines, such as IL-1β, IL-17E, and vascular endothelial growth factor A, were increased, and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells. Mechanistically, the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315, as shown by LC‒MS/MS and Co-IP, and resulted in activation of the ERK3/IL-17E pathway. Overall, our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.

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Demethylation of miR-34a upregulates expression of membrane palmitoylated proteins and promotes the apoptosis of liver cancer cells

Cited by 8 publications

References 32 publications

Identification of hub genes related to CD4+ memory T cell infiltration with gene co-expression network predicts prognosis and immunotherapy effect in colon adenocarcinoma

Identification of hub genes related to CD4+ memory T cell infiltration with gene co-expression network predicts prognosis and immunotherapy effect in colon adenocarcinoma

Single-cell and WGCNA uncover a prognostic model and potential oncogenes in colorectal cancer

A de novo missense mutation in MPP2 confers an increased risk of Vogt–Koyanagi–Harada disease as shown by trio-based whole-exome sequencing

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