Identification of hub genes associated with RNAi-induced silencing of XIAP through targeted proteomics approach in MCF7 cells

Gholizadeh, Mehdi Agha; Shamsabadi, Fatemeh T.; Yamchi, Ahad; Golalipour, Masoud; Jhingan, Gagan Deep; Shahbazi, Majid

doi:10.1186/s13578-020-00437-9

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…Our ndings in this study corroborated previous investigations that have explored the activity of HSPs in cancer-related pathways [29]. The biological function of these family members in apoptosis induction was well described [30].…”

Section: Discussionsupporting

confidence: 90%

Proteomics Analysis Identified Hub Genes Associated With RNAi-Induced Silencing of G1 Cyclins in MDA-MB-231 Cells

Shamsabadi¹,

Eidgahi²,

Yamchi³

et al. 2020

Preprint

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Background: The G1 cyclins are the most potent candidates in the pathogenesis of breast cancer. This study was designed to analyze the synergistic effect of G1 cyclins silencing on the proliferation of breast cancer cells and to identify G1 cyclins-molecular targets by proteomics approach.Methods: The MDA-MB-231 cells were transfected by a dual shRNA vector targeting G1 cyclins through a bidirectional survivin promoter. Silencing efficacy and cell proliferation were evaluated by real-time PCR, Western blot, and MTS assays, respectively. The protein expression profile was evaluated by 2D gel electrophoresis and mass spectroscopy. Further, bioinformatics tools were applied to identify the molecular targets by G1 cyclins and their possible biological consequences.Results: In response to G1 cyclins silencing, the proliferation of cells exposed to the dual shRNA vector decreased significantly at 72 h post-transfection. The reduction of G1 cyclins proteins was following their mRNA expression level as well. Protein signature of cells was altered in response to the silencing of G1 cyclins, 13 up-regulated, and seven down-regulated. Network analysis of G1 cyclins-regulated proteins identified ACTB, HSP90AA1, ALB, and HSPA5 as the hub genes according to the degree method.The regulated proteins by G1 cyclins participate in cancer-related pathways such as PI3K-Akt signaling pathway and pathways in cancer (HSP90AA1; HSP90AB1; HSP9B1), HIF-1 signaling pathway (LDHA; ALDOA; PGK1), apoptosis and proteoglycans in cancer (ACTB).Conclusions: We identified the G1 cyclins-regulated proteins and their mode of action in the pathogenesis of breast cancer. Our findings suggested that G1 cyclins participate in various biological functions. Meanwhile, it offers a new perception of the interactions among G1 cyclins-regulated proteins to identify targeted treatment. It follows-up research in the field of breast cancer.

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Section: Discussionsupporting

confidence: 90%

Proteomics Analysis Identified Hub Genes Associated With RNAi-Induced Silencing of G1 Cyclins in MDA-MB-231 Cells

Shamsabadi¹,

Eidgahi²,

Yamchi³

et al. 2020

Preprint

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“…HSPA9 (Heat Shock Protein Family A (Hsp70) Member 9) is an important apolipoprotein interacting protein. HSPA9 overexpression prevents the import of apoptotic proteins into the nucleus for proapoptotic activity ( Gholizadeh et al, 2020 ). FASN (Fatty Acid Synthase)-mediated lipid metabolism contributes to regulating apoptosis and steroidogenesis ( Liu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis Related Genes in Ischemic and Idiopathic Cardiomyopathy: Screening for Potential Pharmacological Targets

Jiang

Chen

Chao

et al. 2022

Front. Cell Dev. Biol.

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Background: Ferroptosis is a new form of cell death recently discovered that is distinct from apoptosis, necrosis and autophagy. This article is expected to provide a new direction for the treatment of cardiomyopathy in the future by screening potential drug targets associated with ferroptosis.Methods: Differential expression analysis of GSE5406 from the Gene Expression Omnibus (GEO) database was performed using the GEO2R tool. Functional annotation of ferroptosis related genes was also performed. Then we constructed protein-protein interaction networks and identified hub genes using Cytoscape. The candidates for pharmacological compounds targeting the hub genes were screened by cMap.Results: Totally 15 ferroptosis related genes (4 upregulated and 11 downregulated) for ischemic cardiomyopathy and 17 ferroptosis related genes (13 upregulated and 4 downregulated) for idiopathic cardiomyopathy were found. The biological processes involved in these genes mainly include negative regulation of apoptotic process, flavonoid metabolic process, response to drug for ischemic cardiomyopathy and cellular response to fibroblast growth factor stimulus, negative regulation of apoptotic process, and response to drug for idiopathic cardiomyopathy. KEGG results showed that these genes were mainly involved in MAPK signaling pathway for ischemic cardiomyopathy and PI3K-Akt signaling pathway for idiopathic cardiomyopathy. We generated a co-expression network for hub genes and obtained top 10 medications suggested respectively for ischemic/idiopathic cardiomyopathy.Conclusion: Our study reveals the potential role of ferroptosis related genes in ischemic and idiopathic cardiomyopathy through bioinformatics analysis. The hub genes and potential drugs may become novel biomarkers for prognosis and precision treatment in the future.

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“…The gene silencing technique, such as antisense oligonucleotides (ASOs) and short hairpin RNA (shRNA), could effectively knock down the expressions of interesting genes and is an important strategy for gene therapy against various diseases [ 45 , 46 ]. For instance, Wei et al reported that MALAT1-shRNA treatment alleviated the inflammatory injury after lung transplant ischemia–reperfusion by downregulating IL-8 and inhibiting infiltration and activation of neutrophils [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

et al. 2020

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Background Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4−/− mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

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Identification of hub genes associated with RNAi-induced silencing of XIAP through targeted proteomics approach in MCF7 cells

Cited by 6 publications

References 33 publications

Proteomics Analysis Identified Hub Genes Associated With RNAi-Induced Silencing of G1 Cyclins in MDA-MB-231 Cells

Proteomics Analysis Identified Hub Genes Associated With RNAi-Induced Silencing of G1 Cyclins in MDA-MB-231 Cells

Ferroptosis Related Genes in Ischemic and Idiopathic Cardiomyopathy: Screening for Potential Pharmacological Targets

Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

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