Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis

Hussain, Shahid; Saxena, Sonal; Shrivastava, Sameer; Mohanty, Ashok Kumar; Kumar, Sanjay; Singh, Rajkumar James; Kumar, Abhinav; Wani, Sajad A.; Gandham, Ravi Kumar; Kumar, Naveen; Sharma, Anil Kumar; Tiwari, Ashok Kumar; Singh, Raj Kumar

doi:10.1371/journal.pone.0208656

Cited by 25 publications

(18 citation statements)

References 119 publications

(104 reference statements)

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“…ANXA2 is a member of the calcium-dependent phospholipid-binding protein family and is related to the smooth muscle contraction pathway (29,30). A previous study using Affinity Capture-MS showed that ANXA2 binds to myosin heavy chain 9 protein, which is one of the downstream proteins in the Rho GTPase regulatory pathway (31). Overexpression of RP11-531A24.3 suppressed ANXA2 expression at both mRNA and protein levels compared with controls (Fig.…”

Section: Rp11-531a243 Suppresses the Migration And Proliferationmentioning

confidence: 86%

lncRNA RP11‑531A24.3 inhibits the migration and proliferation of vascular smooth muscle cells by downregulating ANXA2 expression

Cai

et al. 2021

Exp Ther Med

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A complete understanding of the behavioral influence and phenotypic transition of vascular smooth muscle cells, as well as the effects of the characteristics of these cells on the physiological and pathological processes of atherosclerosis, is crucial if new therapeutic targets for atherosclerosis are to be identified. In the present study, the long non-coding RNA RP11-531A24.3 was identified to be expressed at low levels in plaque tissues through screening a microarray for differentially expressed genes. The functional experimental results suggested that RP11-531A24.3 reduced the viability and inhibited the migration of human aortic vascular smooth muscle cells (HA-VSMCs). RNA antisense purification-mass spectrometry was used to identify the RNA-binding proteins (RBPs) for RP11-531A24.3. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the pathway with the highest degree of association with RP11-531A24.3 RBPs was related to cell migration. The reduced migration and viability mediated by RP11-531A24.3 overexpression was more significantly suppressed after annexin 2 (ANXA2) depletion in RP11-531A24.3-overexpressing HA-VSMCs. Culture of HA-VSMCs under hypoxic conditions (1% O 2 ) reduced the expression of RP11-531A24.3, and enhanced the protein expression of ANXA2 and HIF-1α, while knockdown of ANXA2 downregulated the protein expression of HIF-1α.These results suggested that RP11-531A24.3 regulated the proliferation and migration of HA-VSMCs through ANXA2 expression, and hypoxia may be an external factor in the regulation of RP11-531A24.3 and its downstream targets.

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Section: Rp11-531a243 Suppresses the Migration And Proliferationmentioning

confidence: 86%

lncRNA RP11‑531A24.3 inhibits the migration and proliferation of vascular smooth muscle cells by downregulating ANXA2 expression

Cai

et al. 2021

Exp Ther Med

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“…For example, CDC73 is a tumor suppressor, which can prevent cells from growing and dividing too fast or uncontrolled, and is closely related to parathyroid carcinoma ( Cetani et al, 2019 ). CDC123 is a cell division cycle protein, and the regulatory effects of the entire cell cycle process can be stopped in one of the normal stages (G1, S, G2, M).CDC123 is highly expressed in choriocarcinoma ( Hussain et al, 2018 ). B4GALT1 is one of the seven β -1,4-galactosyltransferase (beta4galt) genes.…”

Section: Discussionmentioning

confidence: 99%

Exploring the potential biomarkers for prognosis of glioblastoma via weighted gene co-expression network analysis

Zhang

Zhou

Liu

et al. 2022

PeerJ

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Background Glioblastoma (GBM) is the most common malignant tumor in the central system with a poor prognosis. Due to the complexity of its molecular mechanism, the recurrence rate and mortality rate of GBM patients are still high. Therefore, there is an urgent need to screen GBM biomarkers to prove the therapeutic effect and improve the prognosis. Results We extracted data from GBM patients from the Gene Expression Integration Database (GEO), analyzed differentially expressed genes in GEO and identified key modules by weighted gene co-expression network analysis (WGCNA). GSE145128 data was obtained from the GEO database, and the darkturquoise module was determined to be the most relevant to the GBM prognosis by WGCNA (r = − 0.62, p = 0.01). We performed enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the interaction activity in the selected modules. Then Kaplan-Meier survival curve analysis was used to extract genes closely related to GBM prognosis. We used Kaplan-Meier survival curves to analyze the 139 genes in the darkturquoise module, identified four genes (DARS/GDI2/P4HA2/TRUB1) associated with prognostic GBM. Low expression of DARS/GDI2/TRUB1 and high expression of P4HA2 had a poor prognosis. Finally, we used tumor genome map (TCGA) data, verified the characteristics of hub genes through Co-expression analysis, Drug sensitivity analysis, TIMER database analysis and GSVA analysis. We downloaded the data of GBM from the TCGA database, the results of co-expression analysis showed that DARS/GDI2/P4HA2/TRUB1 could regulate the development of GBM by affecting genes such as CDC73/CDC123/B4GALT1/CUL2. Drug sensitivity analysis showed that genes are involved in many classic Cancer-related pathways including TSC/mTOR, RAS/MAPK.TIMER database analysis showed DARS expression is positively correlated with tumor purity (cor = 0.125, p = 1.07e−02)), P4HA2 expression is negatively correlated with tumor purity (cor =−0.279, p = 6.06e−09). Finally, GSVA analysis found that DARS/GDI2/P4HA2/TRUB1 gene sets are closely related to the occurrence of cancer. Conclusion We used two public databases to identify four valuable biomarkers for GBM prognosis, namely DARS/GDI2/P4HA2/TRUB1, which have potential clinical application value and can be used as prognostic markers for GBM.

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“…The meta-analysis case-control GWAS also revealed a candidate region on Chr 7, with a suggestive SNP within the Vasohibin 2 ( VASH2 ) gene. Among other functions, VASH2 has been reported to be involved in mammary tumour development in dogs [ 21 ] and to enhance angiogenesis in mice [ 22 ]. In a study on soft tissue gene expression in CHD, the biological function “angiogenesis” was enriched by differentially expressed genes between CHD affected and unaffected dogs [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association studies for canine hip dysplasia in single and multiple populations – implications and potential novel risk loci

et al. 2021

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Background Association mapping studies of quantitative trait loci (QTL) for canine hip dysplasia (CHD) can contribute to the understanding of the genetic background of this common and debilitating disease and might contribute to its genetic improvement. The power of association studies for CHD is limited by relatively small sample numbers for CHD records within countries, suggesting potential benefits of joining data across countries. However, this is complicated due to the use of different scoring systems across countries. In this study, we incorporated routinely assessed CHD records and genotype data of German Shepherd dogs from two countries (UK and Sweden) to perform genome-wide association studies (GWAS) within populations using different variations of CHD phenotypes. As phenotypes, dogs were either classified into cases and controls based on the Fédération Cynologique Internationale (FCI) five-level grading of the worst hip or the FCI grade was treated as an ordinal trait. In a subsequent meta-analysis, we added publicly available data from a Finnish population and performed the GWAS across all populations. Genetic associations for the CHD phenotypes were evaluated in a linear mixed model using 62,089 SNPs. Results Multiple SNPs with genome-wide significant and suggestive associations were detected in single-population GWAS and the meta-analysis. Few of these SNPs overlapped between populations or between single-population GWAS and the meta-analysis, suggesting that many CHD-related QTL are population-specific. More significant or suggestive SNPs were identified when FCI grades were used as phenotypes in comparison to the case-control approach. MED13 (Chr 9) and PLEKHA7 (Chr 21) emerged as novel positional candidate genes associated with hip dysplasia. Conclusions Our findings confirm the complex genetic nature of hip dysplasia in dogs, with multiple loci associated with the trait, most of which are population-specific. Routinely assessed CHD information collected across countries provide an opportunity to increase sample sizes and statistical power for association studies. While the lack of standardisation of CHD assessment schemes across countries poses a challenge, we showed that conversion of traits can be utilised to overcome this obstacle.

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Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis

Cited by 25 publications

References 119 publications

lncRNA RP11‑531A24.3 inhibits the migration and proliferation of vascular smooth muscle cells by downregulating ANXA2 expression

lncRNA RP11‑531A24.3 inhibits the migration and proliferation of vascular smooth muscle cells by downregulating ANXA2 expression

Exploring the potential biomarkers for prognosis of glioblastoma via weighted gene co-expression network analysis

Genome-wide association studies for canine hip dysplasia in single and multiple populations – implications and potential novel risk loci

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