Transcriptomics analysis reveals the signal transduction mechanism of brassinolides in tea leaves and its regulation on the growth and development of Camellia sinensis

Abstract Background Brassinosteroids (BRs) are a type of sterol plant hormone that play an important role in various biochemical and physiological reactions such as promoting cell growth, increasing biomass, and improving stress resistance. Results To investigate the regulatory and molecular mechanism of BRs on the growth and development of tea plants (Camellia sinensis L.), changes in cell structure and gene expression levels of tea leaves treated with exogenous BRs were analyzed by electron microscopy and high-throughput Illumina RNA-Seq technology. The results showed that the number of starch granules in the chloroplasts and lipid globules increased and thylakoids expanded after BR treatment compared with the control. Transcriptome analysis showed that in the four BR treatments (CAA: BR treatment for 3 h, CAB: BR treatment for 9 h, CAC: BR treatment for 24 h, and CAD: BR treatment for 48 h), 3861 (1867 upregulated and 1994 downregulated), 5030 (2461 upregulated and 2569 downregulated), 1626 (815 upregulated and 811 downregulated), and 2050 (1004 upregulated and 1046 downregulated) differentially expressed genes were detected, respectively, compared with CAK (BR treatment for 0 h). Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, metabolic pathway enrichment analysis showed that the differentially expressed genes of CAA vs. CAK, CAB vs. CAK, CAC vs. CAK, and CAD vs. CAK significantly enriched the functional categories of signal transduction, cell cycle regulation, and starch, sucrose, and flavonoid biosynthesis and metabolism pathways. We also found that after spraying BR, the key genes for caffeine synthesis were downregulated. The results of qRT-PCR coincided with the findings of transcriptomic analysis. Conclusions The present study improved our understanding of the effects of BRs on the growth and development of tea leaves and laid the foundation for the in-depth analysis of signal transduction pathways of BRs in tea leaves.

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Expression and analysis of zinc finger family gene in Lenzites gibbosa

Journal of Forestry Research ◽

10.1007/s11676-019-01044-2 ◽

2019 ◽

Vol 31 (5) ◽

pp. 1889-1898

Author(s):

Jun Zhang ◽

Yujie Chi ◽

Shuxuan Li ◽

Jian Zhang ◽

Jie Chen

Keyword(s):

Endoplasmic Reticulum ◽

Differentially Expressed Genes ◽

Zinc Finger ◽

Growth And Development ◽

Zinc Finger Protein ◽

Enrichment Analysis ◽

Protein Processing ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Go Annotation

Abstract Zinc finger transcription factors play significant roles in the growth and development of plant and animal, but their function remains obscure in fungi. Lenzites gibbosa mycelia were extracted and sequenced by transcriptome analysis after growing on sawdust at different times to support mycelial growth of L. gibbosa in a nutrient matrix. Data bases used for analysis were the Kyoto encyclopedia of genes and genomes (KEGG) annotation, the cluster of orthologous groups of proteins (COG) and gene ontology (GO) annotation. Zinc finger class genes related to the growth and development of L. gibbosa were screened. GO annotation and enrichment analysis of differentially expressed genes were carried out. A total of 114.55 Gb Clean Data were obtained from the L. gibbosa transcriptome. The average Clean Data in each sample was 6.16 Gb. The relative efficiency of reads between each sample and the reference genome was 88.5% to 91.4%. The COG analysis showed that most zinc finger protein genes were related to replication, recombination and repair function. GO enrichment analysis showed that the expressed genes involved in cellular process, cell part and binding. We identified seventy-two expressed genes including seven up-regulated genes and sixty-five down-regulated genes by applying DESeq2 data analysis software. By comparing the significantly expressed genes with KEGG database, 66 annotated sequences were obtained, and 35 primary metabolic pathways were annotated. Pathway enrichment analysis showed that differentially expressed genes were significantly enriched in protein processing in endoplasmic reticulum and ubiquitin-mediated proteolysis pathways. Gene_11750 and gene_5266 are highly correlated with the growth and development of L. gibbosa and are closely related to protein processing in endoplasmic reticulum and ubiquitin-mediated proteolysis pathway. According to gene functional analysis, seven important differentially expressed genes related to the growth and development of L. gibbosa were identified.

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Lipidomics profiling of goose granulosa cell model of stearoyl-CoA desaturase function identifies a pattern of lipid droplets associated with follicle development

Cell & Bioscience ◽

10.1186/s13578-021-00604-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xin Yuan ◽

Shenqiang Hu ◽

Liang Li ◽

Chunchun Han ◽

Hehe Liu ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Lipid Droplets ◽

Cell Model ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Follicle Development ◽

Microscopy Analysis ◽

Stearoyl Coa Desaturase ◽

Underlying Mechanisms

Abstract Background Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese. Results Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism. Conclusions This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.

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AB0005 IDENTIFICATION OF KEY GENES AND PATHWAYS FOR PSORIASIS BASED ON GEO DATABASES BY BIOINFORMATICS ANALYSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1773 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1037.2-1038

Author(s):

X. Sun ◽

S. X. Zhang ◽

S. Song ◽

T. Kong ◽

C. Zheng ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathways ◽

Differentially Expressed Genes ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Shanxi Province ◽

Receptor Interaction ◽

Term Therapy ◽

Pathway Enrichment Analysis ◽

Key Genes

Background:Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both, and also has a strong genetic predisposition and autoimmune pathogenic traits1. The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. And it’s also a chronic relapsing disease, which often necessitates a long-term therapy2.Objectives:To investigate the molecular mechanisms of psoriasis and find the potential gene targets for diagnosis and treating psoriasis.Methods:Total 334 gene expression data of patients with psoriasis research (GSE13355 GSE14905 and GSE30999) were obtained from the Gene Expression Omnibus database. After data preprocessing and screening of differentially expressed genes (DEGs) by R software. Online toll Metascape3 was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. Interactions of proteins encoded by DEGs were discovered by Protein-protein interaction network (PPI) using STRING online software. Cytoscape software was utilized to visualize PPI and the degree of each DEGs was obtained by analyzing the topological structure of the PPI network.Results:A total of 611 DEGs were found to be differentially expressed in psoriasis. GO analysis revealed that up-regulated DEGs were mostly associated with defense and response to external stimulus while down-regulated DEGs were mostly associated with metabolism and synthesis of lipids. KEGG enrichment analysis suggested they were mainly enriched in IL-17 signaling, Toll-like receptor signaling and PPAR signaling pathways, Cytokine-cytokine receptor interaction and lipid metabolism. In addition, top 9 key genes (CXCL10, OASL, IFIT1, IFIT3, RSAD2, MX1, OAS1, IFI44 and OAS2) were identified through Cytoscape.Conclusion:DEGs of psoriasis may play an essential role in disease development and may be potential pathogeneses of psoriasis.References:[1]Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7 [published Online First: 2015/05/31].[2]Zhang YJ, Sun YZ, Gao XH, et al. Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis. Mol Med Rep 2019;20(1):225-35. doi: 10.3892/mmr.2019.10241 [published Online First: 2019/05/23].[3]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

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Transcriptome Analysis of Differentially Expressed mRNA Related to Pigeon Muscle Development

Animals ◽

10.3390/ani11082311 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2311

Author(s):

Hao Ding ◽

Yueyue Lin ◽

Tao Zhang ◽

Lan Chen ◽

Genxi Zhang ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Differentially Expressed Genes ◽

Growth And Development ◽

Muscle Development ◽

Expression Patterns ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Growth Stages ◽

Gene Expression And Regulation

The mechanisms behind the gene expression and regulation that modulate the development and growth of pigeon skeletal muscle remain largely unknown. In this study, we performed gene expression analysis on skeletal muscle samples at different developmental and growth stages using RNA sequencing (RNA−Seq). The differentially expressed genes (DEGs) were identified using edgeR software. Weighted gene co−expression network analysis (WGCNA) was used to identify the gene modules related to the growth and development of pigeon skeletal muscle based on DEGs. A total of 11,311 DEGs were identified. WGCNA aggregated 11,311 DEGs into 12 modules. Black and brown modules were significantly correlated with the 1st and 10th day of skeletal muscle growth, while turquoise and cyan modules were significantly correlated with the 8th and 13th days of skeletal muscle embryonic development. Four mRNA−mRNA regulatory networks corresponding to the four significant modules were constructed and visualised using Cytoscape software. Twenty candidate mRNAs were identified based on their connectivity degrees in the networks, including Abca8b, TCONS−00004461, VWF, OGDH, TGIF1, DKK3, Gfpt1 and RFC5, etc. A KEGG pathway enrichment analysis showed that many pathways were related to the growth and development of pigeon skeletal muscle, including PI3K/AKT/mTOR, AMPK, FAK, and thyroid hormone pathways. Five differentially expressed genes (LAST2, MYPN, DKK3, B4GALT6 and OGDH) in the network were selected, and their expression patterns were quantified by qRT−PCR. The results were consistent with our sequencing results. These findings could enhance our understanding of the gene expression and regulation in the development and growth of pigeon muscle.

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Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Hashimoto’s Thyroiditis

10.21203/rs.3.rs-1023446/v1 ◽

2021 ◽

Author(s):

Li Guoquan ◽

Du Junwei ◽

He Qi ◽

Fu Xinghao ◽

Ji Feihong ◽

...

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Inflammatory Responses ◽

Expression Profiles ◽

Treatment Options ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Chronic Lymphocytic Thyroiditis ◽

Hub Genes

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.

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A competing endogenous RNA mechanism in glioblastoma is investigated by bioinformatics analysis

10.21203/rs.2.21101/v1 ◽

2020 ◽

Author(s):

Jinsheng Wang ◽

Yutao Wang ◽

Lei Gao ◽

Yuhua Zhao ◽

Junhua Liu ◽

...

Keyword(s):

Signaling Pathway ◽

Differentially Expressed Genes ◽

Lupus Erythematosus ◽

Bioinformatics Analysis ◽

Enrichment Analysis ◽

Dendritic Cell Maturation ◽

Vital Role ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

P53 Signaling

Abstract Background Glioblastoma (GBM) is the most aggressive and most lethal primary malignant brain tumor, the 5-year survival rate of which is less than 5%. Novel potential molecular and mechanism of GBM need to investigate.Materials and methods Microarray data of GSE15824 was downloaded from GEO. Differentially expressed genes and lncRNAs were screened by Limma package in R studio, and pathway enrichment analysis was performed by clusterprofiler package in R studio and IPA. The ceRNA mechanism was analyzed and predicted by several kinds of online public databases.ResultsThere were 567 differentially expressed genes and 121 differentially expressed lncRNAs in GBM. And differentially expressed genes were mainly enriched in Tuberculosis, Staphylococcus aureus infection, Systemic lupus erythematosus, Basal cell carcinoma, TGF-beta signaling pathway and p53 signaling pathway. Besides, Neuroinflammation signaling pathway, Role of NFAT in regulation of the immune response, and Dendritic cell maturation were significantly activated in GBM. According to the analysis of target miRNAs of SEM4D and OSER1-AS1, a possible ceRNA mechanism OSER1-AS1/hsa-miR-520h/SEMA4D axis was predicted in GBM.Conclusion Bioinformatics analysis was employed to analyze GSE15824 chip, and predict the potential mechanism. The results revealed that the ceRNA mechanism, OSER1-AS1/hsa-miR-520h/SEMA4D axis, might play a vital role in GBM.

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VIRdb: a comprehensive database for interactive analysis of genes/proteins involved in the pathogenesis of vitiligo

PeerJ ◽

10.7717/peerj.9119 ◽

2020 ◽

Vol 8 ◽

pp. e9119

Author(s):

Priyansh Srivastava ◽

Alakto Choudhury ◽

Mehak Talwar ◽

Sabyasachi Mohanty ◽

Priyanka Narad ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Protein Level ◽

Skin Color ◽

Systems Approach ◽

Basal Layer ◽

Interaction Network ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Gene Interaction Network

Vitiligo is a chronic asymptomatic disorder affecting melanocytes from the basal layer of the epidermis which leads to a patchy loss of skin color. Even though it is one of the neglected disease conditions, people suffering from vitiligo are more prone to psychological disorders. As of now, various studies have been done in order to project auto-immune implications as the root cause. To understand the complexity of vitiligo, we propose the Vitiligo Information Resource (VIRdb) that integrates both the drug-target and systems approach to produce a comprehensive repository entirely devoted to vitiligo, along with curated information at both protein level and gene level along with potential therapeutics leads. These 25,041 natural compounds are curated from Natural Product Activity and Species Source Database. VIRdb is an attempt to accelerate the drug discovery process and laboratory trials for vitiligo through the computationally derived potential drugs. It is an exhaustive resource consisting of 129 differentially expressed genes, which are validated through gene ontology and pathway enrichment analysis. We also report 22 genes through enrichment analysis which are involved in the regulation of epithelial cell differentiation. At the protein level, 40 curated protein target molecules along with their natural hits that are derived through virtual screening. We also demonstrate the utility of the VIRdb by exploring the Protein–Protein Interaction Network and Gene–Gene Interaction Network of the target proteins and differentially expressed genes. For maintaining the quality and standard of the data in the VIRdb, the gold standard in bioinformatics toolkits like Cytoscape, Schrödinger’s GLIDE, along with the server installation of MATLAB, are used for generating results. VIRdb can be accessed through “http://www.vitiligoinfores.com/”.

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Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML

Scientific Reports ◽

10.1038/s41598-021-91864-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Parastoo Modarres ◽

Farzaneh Mohamadi Farsani ◽

Amir Abas Nekouie ◽

Sadeq Vallian

Keyword(s):

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Meta Analysis ◽

Regulatory Gene ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Jnk Pathway ◽

Gene Signatures ◽

Cellular Apoptosis

AbstractThe pathways and robust deregulated gene signatures involved in AML chemo-resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistance phenotype. In this study using gene set enrichment approach, deregulated genes and pathways associated with relapse after chemotherapy were investigated in AML samples. Five AML libraries compiled from GEO and ArrayExpress repositories were used to identify significantly differentially expressed genes between chemo-resistance and chemo-sensitive groups. Functional and pathway enrichment analysis of differentially expressed genes was performed to assess molecular mechanisms related to AML chemotherapeutic resistance. A total of 34 genes selected to be differentially expressed in the chemo-resistance compared to the chemo-sensitive group. Among the genes selected, c-Jun, AKT3, ARAP3, GABBR1, PELI2 and SORT1 are involved in neurotrophin, estrogen, cAMP and Toll-like receptor signaling pathways. All these pathways are located upstream and regulate JNK signaling pathway which functions as a key regulator of cellular apoptosis. Our expression data are in favor of suppression of JNK pathway, which could induce pro-apoptotic gene expression as well as down regulation of survival factors, introducing this pathway as a key regulator of drug-resistance development in AML.

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Deciphering Expression Profiling and Functional Signatures of Individualized Obesity-Associated Genes in Ossification of Ligamentum Flavum Through RNA-Sequence Data Mining

10.21203/rs.3.rs-955257/v1 ◽

2021 ◽

Author(s):

Baoliang Zhang ◽

Lei Yuan ◽

Guanghui Chen ◽

Xi Chen ◽

Xiaoxi Yang ◽

...

Keyword(s):

Correlation Analysis ◽

Signaling Pathways ◽

Differentially Expressed Genes ◽

Immune Cells ◽

Ligamentum Flavum ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Hub Genes ◽

Ossification Of Ligamentum Flavum

Abstract Background: Obese individuals predispose to ossification of ligamentum flavum (OLF), whereas the underlying connections between obesity phenotype and OLF pathomechanism are not fully understood, especially during early life. This study aimed to explore obesity-associated genes and their functional signatures in OLF. Methods: Gene microarray expression data related to OLF were downloaded from the GSE106253 dataset in the Gene Expression Omnibus (GEO) database. The potential obesity-related differentially expressed genes (ORDEGs) in OLF were screened. Then, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for these genes. Furthermore, protein-protein interactions (PPI) were used to identify hub ORDEGs, and Metascape was used to further verify the key signaling pathways and immune-related function signatures of hub ORDEGs. Finally, correlation analysis of hub ORDEGs and identified OLF-related infiltrating immune cells (OIICs) was constructed to understand the possible mechanical link among obesity, immune response and OLF. Results: OLF-related differentially expressed genes and 2051 obesity-related genes from four databases were intersected to obtain 99 ORDEGs, including 54 upregulated and 55 downregulated genes. GO and KEGG analysis revealed that these genes were mainly involved in metabolism, inflammation and immune-related biological functions and pathways. A PPI network was established to determine 14 hub genes (AKT1, CCL2, CCL5, CXCL2, ICAM1, IL10, MYC, PTGS2, SAA1, SOCS1, SOCS3, STAT3, TNFRSF1B and VEGFA). The co-expression network demonstrated that this module was associated with cellular response to biotic stimulus, regulation of inflammatory response, regulation of tyrosine phosphorylation of STAT protein. Furthermore, Metascape functional annotations showed that hub genes were mainly involved in receptor signaling pathway via JAK-STAT, response to TNF and regulation of defense response, and their representative enriched pathways were TNF, adipocytokine and JAK-STAT signaling pathways. Subgroup analysis indicated that T cell activation might be potential immune function processes involved, and correlation analysis revealed that cDCs, memory B-cells and preadipocytes were highly correlated infiltrating immune cells. Conclusions: Our study deciphered individualized obesity-associated gene signature for the first time, which may facilitate exploring the underlying cellular and molecular pathogenesis and novel therapeutic targets of obesity-related early-onset OLF.

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Suppression of JNK Pathway as a Novel Regulator of Chemo-Resistance in AML: A Meta-Analysis of Gene Signatures and Key Pathways

10.21203/rs.3.rs-154119/v1 ◽

2021 ◽

Author(s):

Parastoo Modarres ◽

Farzaneh Mohammadi Farsani ◽

AmirAbas Nekouie ◽

Sadeq Vallian

Keyword(s):

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Meta Analysis ◽

Regulatory Gene ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Jnk Pathway ◽

Gene Signatures ◽

Cellular Apoptosis

Abstract The pathways and robust deregulated gene signatures involved in AML chemo-resistance are not fully understood. Multiple subgroups of AMLs which are under treatment of various regimens seem to have similar regulatory gene(s) or pathway(s) related to their chemo-resistance phenotype. In this study using gene set enrichment approach, deregulated genes and pathways associated with relapse after chemotherapy were investigated in AML samples. Five AML libraries compiled from GEO and ArrayExpress repositories were used to identify significantly differentially expressed genes between chemo-resistance and chemo-sensitive groups. Functional and pathway enrichment analysis of differentially expressed genes was performed to assess molecular mechanisms related to AML chemotherapeutic resistance. A total of 34 genes were selected to be differentially expressed in chemo-resistance compared to chemo-sensitive group. Among these genes, c-Jun, AKT3, ARAP3, GABBR1, PELI2 and SORT1 are involved in neurotrophin, estrogen, cAMP and Toll-like receptor signaling pathways. All these pathways are located upstream and regulate JNK signaling pathway which functions as a key regulator of cellular apoptosis. Our expression data are in favor of suppression of JNK pathway, which could induce pro-apoptotic gene expression as well as down regulation of survival factors, suggesting this pathway as a novel key regulator of drug-resistance development in AML.

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