Transcriptomic profiling of Dip2a in the neural differentiation of mouse embryonic stem cells.

Introduction: The disconnected-interacting protein 2 homolog A (DIP2A), a member of disconnected-interacting 2 protein family, has been shown to be involved in human nervous system-related mental illness. This protein is highly expressed in the nervous system of mouse. Mutation of mouse DIP2A causes defects in spine morphology and synaptic transmission, autism-like behaviors, and defective social novelty [5], [27], indicating that DIP2A is critical to the maintenance of neural development. However, the role of DIP2A in neural differentiation has yet to be investigated. Objective: To determine the role of DIP2A in neural differentiation, a neural differentiation model was established using mouse embryonic stem cells (mESCs) and studied by using gene-knockout technology and RNA-sequencing-based transcriptome analysis. Results: We found that DIP2A is not required for mESCs pluripotency maintenance, but loss of DIP2A causes the neural differentiation abnormalities in both N2B27 and KSR medium. Functional knockout of Dip2a gene also decreased proliferation of mESCs by perturbation of the cell cycle and profoundly inhibited the expression of a large number of neural development-associated genes which mainly enriched in spinal cord development and postsynapse assembly. Conclusions: The results of this report demonstrate that DIP2A plays an essential role in regulating differentiation of mESCs towards the neural fate.

Loss of Dip2b leads to abnormal neural differentiation from mESCs.

BACKGROUND: Disco-interacting protein 2 homolog B is a member of the Dip2 family encoded by the Dip2b gene. Dip2b is widely expressed in neuro-related tissues and is essential in axonal outgrowth during embryogenesis. METHODS: Dip2b knockout mouse embryonic stem cell line was established by CRISPR/Cas9 gene-editing technology. The commercial kits were utilized to detect cell cycle and growth rate. Flow cytometry, qRT-PCR, immunofluorescence, and RNA-seq were employed for phenotype and molecular mechanism assessment. RESULTS: Our results suggested that Dip2b is dispensable for the pluripotency maintenance of mESCs. Dip2b knockout could not alter the cell cycle and proliferation of mECSs, or the ability to differentiate into three germ layers in vitro. Furthermore, genes associated with axon guidance, channel activity, and synaptic membrane were significantly downregulated during neural differentiation upon Dip2b knockout. CONCLUSIONS: Our results suggest that Dip2b plays an important role in neural differentiation, which will provide a valuable model for studying the exact mechanisms of Dip2b during neural differentiation.

Regulation of adipose tissue development and energy metabolism by VEGFB isoforms.

Obesity is caused by imbalanced energy intake and expenditure. Excessive energy intake and storage in adipose tissues are associated with many diseases. Several studies have demonstrated that vascular growth endothelial factor B (VEGFB) deficiency induces obese phenotypes. However, the roles of VEGFB isoforms VEGFB167 and VEGFB186 in adipose tissue development and function are still not clear. In this study, genetic mouse models of adipose-specific VEGFB167 and VEGFB186 overexpression (aP2-Vegfb167 tg/+and aP2-Vegfb186tg/+) were generated and their biologic roles were investigated. On regular chow, adipose-specific VEGFB186 is negatively associated with white adipose tissues (WATs) and positively regulates brown adipose tissues (BATs). VEGFB186 upregulates energy metabolism and metabolism-associated genes. In contrast, VEGFB167 has a nominal role in adipose development and function. On high-fat diet, VEGFB186 expression can reverse the phenotypes of VEGFB deletion. VEGFB186 overexpression upregulates BAT-associated genes and downregulates WAT-associated genes. VEGFB186 and VEGFB167 have very distinct roles in the regulation of adipose development and energy metabolism. As a key regulator of adipose tissue development and energy metabolism, VEGFB186 may be a target for obesity prevention and treatment.

Photodynamic therapy for skin carcinomas: A systematic review and meta-analysis.

Background: Photodynamic therapy (PDT) is increasingly used for the treatment of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). However, it is unknown whether photodynamic therapy is more effective than other commonly used treatment modalities for these cancers. Purpose: The aim of this study was to determine the relative efficacy and safety of PDT compared with placebo or other interventions for the treatment of skin carcinomas. Methods: Searches were performed in PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases. We included randomized controlled trials comparing the PDT with other interventions in adults skin BCC or SCC that reported on lesion response, recurrence, cosmetic appearance, or safety outcomes. Results: Seventeen unique randomized controlled trials, representing 22 study arms from 21 publications were included. The included trials included 2,166 participants, comparing methyl aminolevulinic (MAL) PDT (six studies) or aminolevulinic acid (ALA) PDT (two studies). Comparators included placebo, surgery, hexaminolevulinic (HAL) PDT, erbium: yttrium-aluminum-garnet ablative factional laser (YAG-AFL) PDT, fluorouracil, and imiquimod. There were few studies available for each comparison. Mantel-Haenszel fixed effects risk ratios were calculated for response, recurrence, cosmetic outcomes, and adverse events. MAL-PDT had similar response rates to surgery, ALA-PDT, fluorouracil and imiquimod at 3- and 12 months post-intervention. The rate of recurrence was similar, showing few differences at 12 months, but at later time points (24-60 months), fewer lesions recurred with surgery and imiquimod than with PDT. PDT also caused more adverse events and pain than other interventions. However, PDT treatment was more likely to receive a "good" or "excellent" rating for cosmetic appearance than surgery or cryotherapy. Conclusion: This systematic review and meta-analysis demonstrates that the choice of treatment modality for BCC or SCC is best chosen in the context of the location and size of the lesion, the socioeconomic circumstances of the patient, as well as the patient's preferences. We call for more high quality studies to be done, in order to enable more reliable interpretations of the data. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=368626, identifier CRD42022368626.

Elevated Placental microRNA-155 Is a Biomarker of a Preeclamptic Subtype.

BACKGROUND: Preeclampsia is a complicated syndrome with marked heterogeneity. The biomarker-based classification for this syndrome is more constructive to the targeted prevention and treatment of preeclampsia. It has been reported that preeclamptic patients had elevated microRNA-155 (miR-155) in placentas or circulation. Here, we investigated the characteristics of patients with high placental miR-155 (pl-miR-155). METHODS: Based on the 95th percentile (P95) of pl-miR-155 in controls, preeclamptic patients were divided into high miR-155 group (≥P95) and normal miR-155 group (

Heterozygous loss of Dip2B enhances tumor growth and metastasis by altering immune microenvironment.

Cancer is caused by abnormal cell growth and metastasis to other tissues. Development of cancers is complex and underlining mechanisms are mostly unknown. Disco-interacting protein 2 homolog B (DIP2B) is a member of Dip2. There have been reports suggesting that Dip2B may participate in tumor growth and development. However, direct link between DIP2B and cancer development is missing. In this study, Dip2btm1a/+ heterozygous knockout mouse model was used to investigate tumor growth and metastasis. Results show that one allele knockout of Dip2B significantly promoted tumor growth and metastasis, decreased tumor cell apoptosis and reduced immune cell infiltration in tumors, most likely by altering immune system that includes reduction of macrophage and cytotoxic T-cells infiltration into tumor microenvironment.

Transcriptomic profiling of mice brain under Bex3 regulation.

BEX family genes are expressed in various tissues and play significant roles in neuronal development. A mouse model of Bex3 gene knock-out was generated in this study, using the CRISPR-Cas9 system. Transcriptomic analysis of the brain was performed to identify genes and pathways under Bex3 regulation. Essential biological functions under the control of Bex3 related to brain development were identified. Ninety-five genes were differentially expressed under Bex3-/- regulation, with 53 down and 42 up. Among down-regulated genes, LOC102633156 is a member of zf-C2H2, Xlr3a is an X-linked lymphocyte regulated gene, LOC101056144 is a hippocampal related gene, 2210418O10Rik and Fam205a3 are cortex related genes. Among the upregulated genes, Zfp967 is a zf protein, Tgtp2 is a T cell-specific regulator, Trpc2 is a neuron-related gene, and Evi2 is related to NF1. A total of 34 KEGG disease terms were identified under the Bex3-/- regulation. The most prominent is non-syndromic X-linked mental retardation, where Fgd1 is enriched. Similarly, IRF, MBD, SAND, zf-BED, and zf-C2H2 were significantly enriched transcription factors. A further study is required to confirm and explain each aspect that has been identified in this study.

Analyzing differentially expressed genes and pathways of Bex2-deficient mouse lung via RNA-Seq.

Bex2 is well known for its role in the nervous system, and is associated with neurological disorders, but its role in the lung's physiology is still not reported. To elucidate the functional role of Bex2 in the lung, we generated a Bex2 knock-out (KO) mouse model using the CRISPR-Cas9 technology and performed transcriptomic analysis. A total of 652 genes were identified as differentially expressed between Bex2 -/- and Bex2 +/+ mice, out of which 500 were downregulated, while 152 were upregulated genes. Among these DEGs, Ucp1, Myh6, Coxa7a1, Myl3, Ryr2, RNaset2b, Npy, Enob1, Krt5, Myl2, Hba-a2, and Nrob2 are the most prominent genes. Myl2, was the most downregulated gene, followed by Npy, Hba-a2, Rnaset2b, nr0b2, Klra8, and Ucp1. Tcte3, Eno1b, Zfp990, and Pcdha9 were the most upregulated DEGs. According to gene enrichment analysis, PPAR pathway, cardiac muscle contraction, and cytokine-cytokine receptor interaction were the most enriched pathways. Besides, the nuclear factor-κB signaling pathway and hematopoietic cell linage pathways were also enriched. Chronic obstructive pulmonary disease (COPD) is enriched among KEGG disease pathways. RT-qPCR assays confirmed the RNA-Seq results. This study opens a new window toward the biological functions of Bex2 in different systems.

Analysis of Dip2B Expression in Adult Mouse Tissues Using the LacZ Reporter Gene.

Disconnected (disco)-interacting protein 2 homolog B (Dip2B) is a member of the Dip2 superfamily and plays an essential role in axonal outgrowth during embryogenesis. In adults, Dip2B is highly expressed in different brain regions, as shown by in situ analysis, and may have a role in axon guidance. However, the expression and biological role of Dip2B in other somatic tissues remain unknown. To better visualize Dip2B expression and to provide insight into the roles of Dip2B during postnatal development, we used a Dip2btm1a(wtsi)komp knock-in mouse model, in which a LacZ-Neo fusion protein is expressed under Dip2b promoter and allowed Dip2B expression to be analyzed by X-gal staining. qPCR analyses showed that Dip2b mRNA was expressed in a variety of somatic tissues, including lung and kidney, in addition to brain. LacZ staining indicated that Dip2B is broadly expressed in neuronal, reproductive, and vascular tissues as well as in the kidneys, heart, liver, and lungs. Moreover, neurons and epithelial cells showed rich staining. The broad and intense patterns of Dip2B expression in adult mice provide evidence of the distribution of Dip2B in multiple locations and, thereby, its implication in numerous physiological roles.

CRISPR-mediated base editing in mice using cytosine deaminase base editor 4

BACKGROUND: Many human genetic diseases arise from point mutations. These genetic diseases can theoretically be corrected through gene therapy. However, gene therapy in clinical application is still far from mature. Nearly half of the pathogenic single-nucleotide polymorphisms (SNPs) are caused by G:C>A:T or T:A>C:G base changes and the ideal approaches to correct these mutations are base editing. These CRISPR-Cas9-mediated base editing does not leave any footprint in genome and does not require donor DNA sequences for homologous recombination. These base editing methods have been successfully applied to cultured mammalian cells with high precision and efficiency, but BE4 has not been confirmed in mice. Animal models are important for dissecting pathogenic mechanism of human genetic diseases and testing of base correction efficacy in vivo. Cytidine base editor BE4 is a newly developed version of cytidine base editing system that converts cytidine (C) to uridine (U). RESULTS: In this study, BE4 system was tested in cells to inactivate GFP gene and in mice to introduce single-base substitution that would lead to a stop codon in tyrosinase gene. High percentage albino coat-colored mice were obtained from black coat-colored donor zygotes after pronuclei microinjection. Sequencing results showed that expected base changes were obtained with high precision and efficiency (56.25%). There are no off-targeting events identified in predicted potential off-target sites. CONCLUSIONS: Results confirm BE4 system can work in vivo with high precision and efficacy, and has great potentials in clinic to repair human genetic mutations.

Oxytocin receptor induces mammary tumorigenesis through prolactin/p-STAT5 pathway.

Oxytocin receptor (OXTR) is involved in social behaviors, thermoregulation, and milk ejection, yet little is known about its role in breast cancer. To investigate the role of OXTR in mammary gland development and tumorigenesis, a transgenic mouse model of OXTR overexpression (++Oxtr) was used. Overexpression of OXTR-induced progressive mammary hyperplasia, unexpected milk production, and tumorigenesis in females. OXTR-induced mammary tumors showed ERBB2 upregulation and mixed histological subtypes with predomination of papillary and medullary carcinomas. OXTR overexpression led to an activation of prolactin (PRL)/p-STAT5 pathway and created a microenvironment that promotes mammary-specific tumorigenesis. PRL inhibitor bromocriptine (Br) could mitigate OXTR-driven mammary tumor growth. The study demonstrates Oxtr is an oncogene and a potential drug target for HER2-type breast cancer.

Knockout of Dip2c in murine ES cell line IBMSe001-B-1 by CRISPR/Cas9 genome editing technology.

DIP2 protein contains three members: DIP2A, DIP2B and DIP2C, and are broadly expressed in the nervous system from Drosophila to human during embryonic development. Dip2c gene-associated mutations have been reported in tumors and neuronal diseases. However, the role ofDip2cin the context of mouse embryonic stem (mES) cells has not been explored.To investigate the biological function of Dip2c during early embryo development, we generated Dip2c-/- mES line using a CRISPR/Cas9 system. This cell line has contributed to further investigation of molecular mechanism of Dip2c during cell differentiation, as well as a cell model for screening for neurogenic drug and cancer clinical cure.

Effect of low VEGF on lung development and function.

Vascular endothelial growth factor (VEGF) is important for lung development and function but ideal mouse models are limited to decipher the quantitative relationship between VEGF expression levels and its proper development and pathogenesis. Human SPC promoter has been used to faithfully express genes or cDNAs in the pulmonary epithelium in many transgenic mouse models. In the study, a mouse model of lung-specific and reversible VEGF repression (hspc-rtTRtg/+/VegftetO/tetO) was generated. Human SPC promoter was used to drive lung-specific rtTR expression, a cDNA coding for doxycycline-regulated transcription repression protein. By crossing with VegftetO/tetO mice, that has tetracycline operator sequences insertion in 5'-UTR region, it allows us to reversibly inhibit lung VEGF transcription from its endogenous level through doxycycline food, water or injection. The tissue-specific inhibition of VEGF is used to mimic abnormal expression levels of VEGF in lung. Reduced VEGF expression in lung is confirmed by quantitative real time PCR and immunoblotting. Lung development and structure was analyzed by histology analysis and found significantly affected under low VEGF. The pulmonary epithelium and alveolarization are found abnormal with swelling alveolar septum and enlargement of air space. Genome-wide gene expression analysis identified that immune activities are involved in the VEGF-regulated lung functions. The transgenic mouse model can be used to mimic human pulmonary diseases. The mouse model confirms the important regulatory roles of epithelial expressed VEGF in lung development and function. This mouse model is valuable for studying VEGF-regulated lung development, pathogenesis and drug screening under low VEGF expression.

Targeted Disruption of Mouse Dip2B Leads to Abnormal Lung Development and Prenatal Lethality.

Molecular and anatomical functions of mammalian Dip2 family members (Dip2A, Dip2B and Dip2C) during organogenesis are largely unknown. Here, we explored the indispensable role of Dip2B in mouse lung development. Using a LacZ reporter, we explored Dip2B expression during embryogenesis. This study shows that Dip2B expression is widely distributed in various neuronal, myocardial, endothelial, and epithelial cell types during embryogenesis. Target disruption of Dip2b leads to intrauterine growth restriction, defective lung formation and perinatal mortality. Dip2B is crucial for late lung maturation rather than early-branching morphogenesis. The morphological analysis shows that Dip2b loss leads to disrupted air sac formation, interstitium septation and increased cellularity. In BrdU incorporation assay, it is shown that Dip2b loss results in increased cell proliferation at the saccular stage of lung development. RNA-seq analysis reveals that 1431 genes are affected in Dip2b deficient lungs at E18.5 gestation age. Gene ontology analysis indicates cell cycle-related genes are upregulated and immune system related genes are downregulated. KEGG analysis identifies oxidative phosphorylation as the most overrepresented pathways along with the G2/M phase transition pathway. Loss of Dip2b de-represses the expression of alveolar type I and type II molecular markers. Altogether, the study demonstrates an important role of Dip2B in lung maturation and survival.

Global transcriptome study of Dip2B-deficient mouse embryonic lung fibroblast reveals its important roles in cell proliferation and development.

Disco-interacting protein 2 homolog B (Dip2B) is a member of Dip2 family encoded by Dip2b gene. Dip2B has been reported to regulate murine epithelial KIT+ progenitor cell expansion and differentiation epigenetically via exosomal miRNA targeting during salivary gland organogenesis. However, its molecular functions, cellular activities and biological process remain unstudied. Here, we investigated the transcriptome of Dip2B-deficient mouse embryonic lung fibroblasts (MELFs) isolated from E14.5 embryos by RNA-Seq. Expression profiling identified 1369 and 1104 differentially expressed genes (DEGs) from Dip2b-/- and Dip2b+/- MELFs in comparisons to wild-type (Dip2b+/+ ). Functional clustering of DEGs revealed that many gene ontology terms belong to membrane activities such as 'integral component of plasma membrane', and 'ion channel activity', suggesting possible roles of Dip2B in membrane integrity and membrane function. KEGG pathway analysis revealed that multiple metabolic pathways are affected in Dip2b- / - and Dip2b +/ - when compared to Dip2b +/+ MELFs. These include 'protein digestion and absorption', 'pancreatic secretion' and 'steroid hormone synthesis pathway'. These results suggest that Dip2B may play important roles in metabolism. Molecular function analysis shows transcription factors including Hox-genes, bHLH-genes, and Forkhead-genes are significantly down-regulated in Dip2b- / - MELFs. These genes are critical in embryo development and cell differentiation. In addition, Dip2B-deficient MELFs demonstrated a reduction in cell proliferation and migration, and an increase in apoptosis. All results indicate that Dip2B plays multiple roles in cell proliferation, migration and apoptosis during embryogenesis and may participate in control of metabolism. This study provides valuable information for further understanding of the function and regulatory mechanisms of Dip2B.

Brain transcriptome study through CRISPR/Cas9 mediated mouse Dip2c gene knock-out.

Dip2C is highly expressed in brain and many other tissues but its biological functions are still not clear. Genes regulated by Dip2C in brain have never been studied. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems, adaptive immune systems of bacteria and archaea, have been recently developed and broadly used in genome editing. Here, we describe targeted gene deletions of Dip2c gene in mice via CRISPR/Cas9 system and study of brain transcriptome under Dip2C regulation. The CRISPR/Cas9 system effectively generated targeted deletions of Dip2c by pronuclei injection of plasmids that express Cas9 protein and two sgRNAs. We achieved targeted large fragment deletion with efficiencies at 14.3% (1/7), 66.7% (2/3) and 20% (1/5) respectively in 3 independent experiments, averaging 26.7%. The large deletion DNA segments are 160.4 kb (Dip2CΔ160kb), spanning from end of exon 4 to mid of exon 38. A mouse with two base pair deletion was generated from a single sgRNA targeting in exon 4 (Dip2cΔ2bp) by non-homologous end joining (NHEJ). Loss of gene expression for Dip2c mRNA was confirmed by quantitative real-time PCR (qPCR). Dip2C-regulated genes and pathways in brain were investigated through RNAseq of Dip2cΔ2bp. In total, 838 genes were found differentially regulated, with 252 up and 586 down. Gene ontology (GO) analysis indicated that DEGs in brain are enriched in neurological functions including 'memory', 'neuropeptide signaling pathway', and 'response to amphetamine' while KEGG analysis shows that 'neuroactive ligand-receptor interaction pathway' is the most significantly enriched. DEGs Grid2ip, Grin2a, Grin2c, Grm4, Gabbr2, Gabra5, Gabre, Gabrq, Gabra6 and Gabrr2 are among the highly regulated genes by Dip2C. Results confirm Dip2C may play important roles in brain development and function.

Generation of Dip2a homozygous knockout murine ES cell line IBMSe001-A-1 via CRISPR/Cas9 technology.

DIP2A mutation is associated with abnormal brain development and diseases including dyslexia, autism and Alzheimer's disease. However, the role and the involved mechanisms remain unknown. To study the biological function of DIP2A during mESCs neural differentiation in early neural development, we generated a Dip2a homozygous knockout 46C ESC cell line using CRISPR/Cas9 genome editing technology. The eighth exon of Dip2a gene was replaced with PGK-Puro-P2A-mCherry. This 46C-Dip2a KO cell line offers a useful resource to investigate the molecular mechanisms of DIP2A in the process of cell fate determination, as well as a potential source of building disease mouse model.

DIP2B Interacts With α-Tubulin to Regulate Axon Outgrowth.

Axonal development is essential to the establishment of neuronal morphology and circuitry, although the mechanisms underlying axonal outgrowth during the early developmental stages remain unclear. Here, we showed that the conserved disco-interacting protein B (DIP2B) which consists of a DMAP1 domain and a crotonobetaine/carnitine CoA ligase (Caic) domain, is highly expressed in the excitatory neurons of the hippocampus. DIP2B knockout led to excessive axonal outgrowth but not polarity at an early developmental stage. Furthermore, the loss of DIP2B inhibited synaptic transmission for both spontaneous and rapid release in cultured hippocampal neurons. Interestingly, DIP2B function during axonal outgrowth requires tubulin acetylation. These findings reveal a new conserved regulator of neuronal morphology and provide a novel intervention mechanism for neurocognitive disorders.

Adipose vascular endothelial growth factor B is a major regulator of energy metabolism.

Excessive fat accumulation causes obesity and many diseases. Previous study demonstrates VEGFB universal knockout induces obese phenotypes including expansion of white adipose tissue, whitening of brown adipose tissue, increase of fat accumulation and reduction in energy consumption. However, roles of VEGFB in adipose tissues are not clear. In this study, we have generated a mouse model with adipose-specific VEGFB repression using CRISPR/dCas9 system (Vegfb AdipoDown ) and investigated the roles of VEGFB in adipose development and energy metabolism. VEGFB repression induced significant changes in adipose tissue structure and function. Vegfb AdipoDown mice have larger body sizes, larger volume of white adipose tissues than its wild type littermates. Adipose-specific VEGFB repression induced morphological and functional transformation of adipose tissues toward white adipose for energy storage. Metabolic processes are broadly changed in Vegfb AdipoDown adipose tissues including carbohydrate metabolism, lipid metabolism, nucleotide metabolism and amino acid metabolism. We have demonstrated that adipose VEGFB repression can recapitulate most of the phenotypes of the whole body VEGFB knockout mouse. Intriguingly, approximately 50% VEGFB repression in adipose tissues can almost completely mimic the effects of universal Vegfb deletion, suggesting adipose VEGFB is a major regulator of energy metabolism and may be important in prevention and treatment of obesity.

The modification of ferroptosis and abnormal lipometabolism through overexpression and knockdown of potential prognostic biomarker perilipin2 in gastric carcinoma.

BACKGROUND: To investigate the biological relationship, mechanism between perilipin2 and the occurrence, advancement of gastric carcinoma, and explore the mechanism of lipid metabolism disorder leading to gastric neoplasm, and propose that perilipin2 is presumably considered as a potential molecular biomarker of gastric carcinoma. METHODS: RNA-seq was applied to analyze perilipin2 and differentially expressed genes modulated by perilipin2 in neoplastic tissues of both perilipin2 overexpression and knockdown groups in vivo. The mechanism was discovered and confirmed by Rt-qPCR, immunoblotting, immunohistochemistry, staining and microassay, respectively. Cellular function experiments were performed by flow cytometry, CCK8, clonogenic assay, etc. RESULTS: Overexpression and knockdown of perilipin2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. The neoplastic cells with perilipin2-overexpression obtained more conspicuously rapid growth than knockdown group in vivo, and perilipin2 affected the proliferation and apoptosis of gastric carcinoma cells by modulating the related genes:acyl-coa synthetase long-chain family member 3, arachidonate 15-lipoxygenase, microtubule associated protein 1 light chain 3 alpha, pr/set domain 11 and importin 7 that were participated in Ferroptosis pathway. Moreover, RNA-seq indicated perilipin2 was an indispensable gene and protein in the suppression of Ferroptosis caused by abnormal lipometabolism in gastric carcinoma. CONCLUSION: Our study expounded the facilitation of perilipin2 in regulating the proliferation and apoptosis of gastric carcinoma cells by modification in Ferroptosis pathway, and we interpreted that the mechanism of gastric neoplasm caused by obesity, we also discovered that pr/set domain 11 and importin 7 are novel transcription factors relevant to gastric carcinoma. Furthermore, perilipin2 probably serves not only as a diagnostic biomarker, but also a new therapeutic target.