Altered mRNA expression levels of autophagy- and apoptosis-related genes in the FOXO pathway in schizophrenia patients treated with olanzapine

Gu, Shuguang; Cui, Fengwei; Yin, Jiajun; Fang, Chunxia; Liu, Liang

doi:10.1016/j.neulet.2021.135669

Cited by 20 publications

(8 citation statements)

References 31 publications

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“…Previously, a meta-analysis demonstrated that people with SCZ are more likely to have infectious hepatitis, which could be attributed to behavioral, immunological parameters, or both 72 . It is also shown that expression levels of mitogen-activated protein kinase (MAPK) 73 and forkhead box O (FOXO) pathway-related genes 74 are altered in SCZ. Association between relaxin polymorphisms and SCZ also suggests that the relaxin pathway plays a role in the development of SCZ 75 .…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia

Sabaie

Moghaddam

et al. 2021

Sci Rep

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Schizophrenia (SCZ) is a serious psychiatric condition with a 1% lifetime risk. SCZ is one of the top ten global causes of disabilities. Despite numerous attempts to understand the function of genetic factors in SCZ development, genetic components in SCZ pathophysiology remain unknown. The competing endogenous RNA (ceRNA) network has been demonstrated to be involved in the development of many kinds of diseases. The ceRNA hypothesis states that cross-talks between coding and non-coding RNAs, including long non-coding RNAs (lncRNAs), via miRNA complementary sequences known as miRNA response elements, creates a large regulatory network across the transcriptome. In the present study, we developed a lncRNA-related ceRNA network to elucidate molecular regulatory mechanisms involved in SCZ. Microarray datasets associated with brain regions (GSE53987) and lymphoblasts (LBs) derived from peripheral blood (sample set B from GSE73129) of SCZ patients and control subjects containing information about both mRNAs and lncRNAs were downloaded from the Gene Expression Omnibus database. The GSE53987 comprised 48 brain samples taken from SCZ patients (15 HPC: hippocampus, 15 BA46: Brodmann area 46, 18 STR: striatum) and 55 brain samples taken from control subjects (18 HPC, 19 BA46, 18 STR). The sample set B of GSE73129 comprised 30 LB samples (15 patients with SCZ and 15 controls). Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the limma package of the R software. Using DIANA-LncBase, Human MicroRNA Disease Database (HMDD), and miRTarBase, the lncRNA- associated ceRNA network was generated. Pathway enrichment of DEmRNAs was performed using the Enrichr tool. We developed a protein–protein interaction network of DEmRNAs and identified the top five hub genes by the use of STRING and Cytoscape, respectively. Eventually, the hub genes, DElncRNAs, and predictive miRNAs were chosen to reconstruct the subceRNA networks. Our bioinformatics analysis showed that twelve key DEmRNAs, including BDNF, VEGFA, FGF2, FOS, CD44, SOX2, NRAS, SPARC, ZFP36, FGG, ELAVL1, and STARD13, participate in the ceRNA network in SCZ. We also identified DLX6-AS1, NEAT1, MINCR, LINC01094, DLGAP1-AS1, BABAM2-AS1, PAX8-AS1, ZFHX4-AS1, XIST, and MALAT1 as key DElncRNAs regulating the genes mentioned above. Furthermore, expression of 15 DEmRNAs (e.g., ADM and HLA-DRB1) and one DElncRNA (XIST) were changed in both the brain and LB, suggesting that they could be regarded as candidates for future biomarker studies. The study indicated that ceRNAs could be research candidates for investigating SCZ molecular pathways.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia

Sabaie

Moghaddam

et al. 2021

Sci Rep

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“…The increased expression of IL-6 would enhance cell survival and transform cell growth in human malignant cholangiocytes (Meng et al, 2006). Also, the decreased expression of FOXO3A was found in acute SCZ patients (Gu et al, 2021). It is possible that the reduced expression of FOXO3 leads to enhanced IL-6 expression and formed an enhanced immune system.…”

Section: Discussionmentioning

confidence: 99%

Genetic trade‐offs between complex diseases and longevity

Zhang

et al. 2022

Aging Cell

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Longevity was influenced by many complex diseases and traits. However, the relationships between human longevity and genetic risks of complex diseases were not broadly studied. Here, we constructed polygenic risk scores (PRSs) for 225 complex diseases/traits and evaluated their relationships with human longevity in a cohort with 2178 centenarians and 2299 middle‐aged individuals. Lower genetic risks of stroke and hypotension were observed in centenarians, while higher genetic risks of schizophrenia (SCZ) and type 2 diabetes (T2D) were detected in long‐lived individuals. We further stratified PRSs into cell‐type groups and significance‐level groups. The results showed that the immune component of SCZ genetic risk was positively linked to longevity, and the renal component of T2D genetic risk was the most deleterious. Additionally, SNPs with very small p‐values (p ≤ 1x10‐5) for SCZ and T2D were negatively correlated with longevity. While for the less significant SNPs (1x10‐5 < p ≤ 0.05), their effects on disease and longevity were positively correlated. Overall, we identified genetically informed positive and negative factors for human longevity, gained more insights on the accumulation of disease risk alleles during evolution, and provided evidence for the theory of genetic trade‐offs between complex diseases and longevity.

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“…Gu ve ark. birçok çalışmada şizofreni ve diğer psikiyatrik bozuklukları olan hastalarda mTOR geninin bu çalışmamızda olduğu gibi anormal derecede yüksek eksprese olduğunu vurgulamışlardır 46 . Fakat kendilerinin şizofreni hastalarında mTOR geni ekspresyonunu düşük olduğunu göstermişlerdir.…”

Section: Discussionunclassified

Şizofreni hastalarında CYB mtDNA mutasyonları ve PI3K/AKT/mTOR sinyal yolağındaki genlerin ekspresyon durumu

Dirican

Uzunçakmak

Özcan

2022

Cukurova Medical Journal

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Amaç: Bu çalışma, şizofreni hastalarında sitokrom b (CYB) mitokondriyal DNA (mtDNA) mutasyonlarını taramayı ve PI3K/AKT/mTOR sinyal yolağındaki genlerin mRNA ifadelerini analiz etmeyi amaçlamıştır. Gereç ve Yöntem: Bu çalışmada 44 şizofreni hastasından ve 41 sağlıklı bireyden DNA (hasta) ve RNA (hasta ve kontrol) izolasyonu için tam kan alındı. CYB mtDNA mutasyonları için örnekler PCR ile amplifiye edildi ve Sanger DNA dizi analiziyle tanımlandı. PIK3CA, AKT1 ve mTOR genlerinin mRNA ekspresyonu için RT-PCR ve 2-∆∆Ct metodu kullanıldı. Bulgular: Şizofreni hastalarında m.15326 A>G (43/44), m.15452 C>A (5/44), m.15078 A>G (3/44), m.14872 C>T (3/44) ve m.14798 T>C (3/44) en sık rastalanan CYB mtDNA mutasyonlarıydı. İn silico analizler, mutasyonların bir kısmının zararlı, hastalık yapıcı veya benign karakterle ilişkili olduğunu gösterdi. Şizofreni hastalarında PIK3CA, AKT1 ve mTOR genlerinin mRNA ekspresyonu sağlıklı bireylere göre anlamlı derecede yüksekti. PIK3CA ve AKT1 genleri arasında anlamlı orta şiddette pozitif bir korelasyon tespit edildi. Ayrıca ROC analizi ile PIK3CA, AKT1 ve mTOR genlerinin hasta grubunda iyi tanısal güce sahip olduğu belirlendi. ROC analizleri, özellikle PIK3CA'nın şizofreni hastaları için % 80 duyarlılık ve % 63,4 seçicilik ile önemli bir tanı değerine sahip olduğunu gösterdi. Sonuç: Şizofreni hastalarında hem CYB mtDNA mutasyon sıklığı hem de PIK3CA, AKT1 ve mTOR mRNA ekspresyon düzeyi sağlıklı bireylere göre daha yüksekti. Bu mekanizmaları daha geniş şizofreni popülasyonunda çalışmanın hastalığın tanı, tedavi veya prognozunda değerli olabileceğine inanıyoruz.

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Altered mRNA expression levels of autophagy- and apoptosis-related genes in the FOXO pathway in schizophrenia patients treated with olanzapine

Cited by 20 publications

References 31 publications

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia

Bioinformatics analysis of long non-coding RNA-associated competing endogenous RNA network in schizophrenia

Genetic trade‐offs between complex diseases and longevity

Şizofreni hastalarında CYB mtDNA mutasyonları ve PI3K/AKT/mTOR sinyal yolağındaki genlerin ekspresyon durumu

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