A pan-cancer study of selenoprotein genes as promising targets for cancer therapy

Wu, Wentao; Li, Daning; Xue, Feng; Zhao, Fanfan; Li, Chengzhuo; Zheng, Shuai; Lyu, Jun

doi:10.1186/s12920-021-00930-1

Cited by 37 publications

(37 citation statements)

References 75 publications

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“…For example, the RBP CLUH (clustered mitochondria homologue), together with other RBPs, have been shown to regulate the expression of a mitochondrial protein network that become important under conditions of nutrient deprivation (67). Glutathione metabolism is key to the disposition of super-oxides, which are produced at high levels during chemotherapy (68). CRD-BP and its close paralogue, IGF2BP3, have beeen shown to enhance drug resistance for tumor cells (69,70).…”

Section: Comparison Of the Results Of Esp Purification Of Crd-bp Binding Rnas With Other Studiesmentioning

confidence: 99%

Enhanced Immunoprecipitation Techniques for the Identification of RNA Binding Protein Partners: CRD-BP interactions in mammary epithelial cells

Fakhraldeen

et al. 2021

Preprint

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RNA binding proteins (RBPs) regulate expression of large cohorts of RNA species to affect programmatic changes in cellular phenotypes. In order to describe the function of RBPs within a cell, it is key to identify their mRNA binding partners. This is often done by cross-linking nucleic acids to RBPs, followed by chemical release of the nucleic acid fragments for analysis. However, this methodology is lengthy, involves complex processing leading to extraordinary losses, requires large amounts of starting materials, and is prone to artifacts due to the labile nature of mRNA. To evaluate potential alternative technologies, we tested "exclusion-based" purification of immunoprecipitates (oil-based IFAST™ or air-based SLIDE™), and report here that these methods can efficiently, rapidly and specifically isolate RBP-RNA complexes with minimal handling. The analysis starts with >100x less material than for techniques that include cross-linking. Depending on the specific antibody used, 50-100% of starting protein is retrieved, allowing the assay of endogenous levels of RBP instead of tagged and over-expressed ectopic proteins. Isolated protein and nucleic acid components are purified and analyzed using standard techniques to provide a comprehensive portrait of RBP complexes. Using exclusion-based techniques, we show that the mRNA binding partners for CRD-BP/IMP1/IGF2BP1/ZBP1 in cultured mammary epithelial cells are enriched in mRNAs important for de-toxifying superoxides (glutathione metabolic enzymes) and other mRNAs encoding mitochondrial proteins.

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Section: Comparison Of the Results Of Esp Purification Of Crd-bp Binding Rnas With Other Studiesmentioning

confidence: 99%

Enhanced Immunoprecipitation Techniques for the Identification of RNA Binding Protein Partners: CRD-BP interactions in mammary epithelial cells

Fakhraldeen

et al. 2021

Preprint

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“…GPX consists of eight antioxidant enzymes, and their main function is to defend the organism against oxidative stress. A previous study revealed that GPXs have antitumor effects because they block reactive oxygen species (ROS) and regulate the redox signaling system, which plays a key role in tumor growth (Wu et al, 2021). Hydroperoxides stimulate cell proliferation and migration, but excessive hydroperoxides lead to cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Anhydroicaritin Inhibits EMT in Breast Cancer by Enhancing GPX1 Expression: A Research Based on Sequencing Technologies and Bioinformatics Analysis

Shi

Xiao

et al. 2022

Front. Cell Dev. Biol.

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Background: Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. The application of advanced technology has promoted accurate diagnosis and treatment of cancer. Anhydroicaritin (AHI) is a flavonoid with therapeutic potential in BC treatment. The current study aimed to determine AHI’s mechanism in BC treatment via RNA sequencing, comprehensive bioinformatics analysis, and experimental verification.Methods: Network pharmacology and MTT (3-(4,5)-dimethylthiazolyl-3,5- diphenyltetrazolium bromide) experiments were conducted to first confirm AHI’s anti-BC effect. RNA sequencing was performed to identify the genes affected by AHI. Differential expression analysis, survival analysis, gene set enrichment analysis, and immune infiltration analysis were performed via bioinformatics analysis. Western blot analysis, reverse transcription–polymerase chain reaction (RT-PCR) experiment, molecular docking, and drug affinity responsive target stability (DARTS) experiments were also performed to confirm AHI’s direct effect on glutathione peroxidase 1 (GPX1) expression. Confocal immunofluorescence analysis was conducted to verify AHI’s effect on the occurrence and development of epithelial–mesenchymal transition (EMT). Finally, BC nude mouse xenografts were established, and AHI’s molecular mechanism on BC was explored.Results: Network pharmacology results demonstrated that AHI’s therapeutic targets on BC were related to the proliferation, invasion, and metastasis of BC cells. AHI significantly inhibited the proliferation of 4T1 and MDA-MB-231 BC cells in the MTT experiments. RNA sequencing results showed that AHI upregulated the GPX1 expression in the 4T1 and MDA-MB-231 BC cells. Next, bioinformatics analysis revealed that GPX1 is less expressed in BC than in normal breast tissues. Patients with high GPX1 expression levels tended to have prolonged overall survival and disease-free survival than patients with low GPX1 expression levels in BC. Western blot and RT-PCR experiments revealed that AHI increased the protein and mRNA levels of GPX1. Molecular docking and DARTS experiments confirmed the direct binding combination between AHI and GPX1. After the evaluation of the EMT scores of 1,078 patients with BC, we found a potential anti-BC role of GPX1 possibly via suppression of the malignant EMT. The confocal immunofluorescence analysis showed that AHI increased E-cadherin expression levels and reduced vimentin expression levels in BC cells. Animal experiments showed that AHI significantly inhibited tumor growth. AHI also inhibited EMT by enhancing GPX1 and caspase3 cleavage, hence inhibiting EMT markers (i.e., N-cadherin and vimentin) and Ki-67.Conclusion: GPX1 plays a critical role in BC, which may be a biomarker for the prognosis. In addition, AHI suppressed EMT by increasing GPX1 expression, which may serve as a potential therapy for BC treatment.

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“…Regarding the somatic mutations in adjacent normal tissues, we found that somatic mutations in GPX2 and PPDPF initially occurred in normal tissues patients and accumulated in tumors. GPX2 plays a role in protecting cells against oxidative damage ( 56 ), and PPDPF is a probable regulator of exocrine pancreas development ( 57 ). Abnormal expression of GPX2 might facilitate tumorigenesis and result in poor progress in adrenocortical cancer, kidney papillary cell carcinoma, and uveal melanoma ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

“…GPX2 plays a role in protecting cells against oxidative damage ( 56 ), and PPDPF is a probable regulator of exocrine pancreas development ( 57 ). Abnormal expression of GPX2 might facilitate tumorigenesis and result in poor progress in adrenocortical cancer, kidney papillary cell carcinoma, and uveal melanoma ( 56 ). Aberrant PPDPF expression was correlated with poor prognosis in hepatocellular carcinoma ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas

Fang

Sun

et al. 2021

Front. Immunol.

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Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB-TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC.

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A pan-cancer study of selenoprotein genes as promising targets for cancer therapy

Cited by 37 publications

References 75 publications

Enhanced Immunoprecipitation Techniques for the Identification of RNA Binding Protein Partners: CRD-BP interactions in mammary epithelial cells

Enhanced Immunoprecipitation Techniques for the Identification of RNA Binding Protein Partners: CRD-BP interactions in mammary epithelial cells

Anhydroicaritin Inhibits EMT in Breast Cancer by Enhancing GPX1 Expression: A Research Based on Sequencing Technologies and Bioinformatics Analysis

Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas

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