<scp>MYB</scp> sustains hypoxic survival of pancreatic cancer cells by facilitating metabolic reprogramming

Anand, Shashi; Khan, Mohammad Aslam; Zubair, Haseeb; Sudan, Sarabjeet Kour; Vikramdeo, Kunwar Somesh; Deshmukh, Sachin Kumar; Azim, Shafquat; Srivastava, Sanjeev K.; Singh, Seema; Singh, Ajay P.

doi:10.15252/embr.202255643

Cited by 14 publications

(8 citation statements)

References 74 publications

(99 reference statements)

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“…It is worth noting that MYB and STAG1 were found to regulate both DOCK8 and GIMAP5, implying that MYB and STAG1 may exert similar biological functions through these two genes. Anand found that MYB/HIF1α axis is a key regulator of metabolic plasticity and hypoxic survival in pancreatic cancer cells (Anand et al 2023). Giannini et al demonstrated that STAG1 is overexpressed in various tumors of reproductive system cancer and is associated with aberrant activation of the epidermal growth factor (EGF) pathway (Giannini et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Analysis and Regulatory Mechanisms of Platelet-related Genes in Patients with Ischemic Stroke

Shu

et al. 2023

Preprint

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It was found that ischemic stroke (IS) was associated with abnormal platelet activity and thrombosis. However, the potential significance of platelet-related genes (PRGs) in IS still needs to be more thorough. This study extracted IS-related transcriptome datasets from the Gene Expression Omnibus (GEO) database. The target genes were obtained by intersecting the differentially expressed genes (DEGs), the module genes related to IS, and PRGs, where the key genes of IS were screened by two machine learning algorithms. The key genes-based diagnostic model was constructed. Gene set enrichment analysis (GSEA) and the immune microenvironment analyses were analyzed targeting key genes in IS. The co-expression, TF-mRNA, and competitive endogenous RNAs (ceRNA) regulatory networks were constructed to reveal the potential regulation of key genes. Potential drugs targeting key genes were predicted as well. Totals of eight target genes were obtained and were associated with immune-related functions. Four platelet-related key genes were acquired, which were related to immunity and energy metabolism. The abnormal expressions of DOCK8, GIMAP5, ICOS were determined by the quantitative real-time Polymerase Chain Reaction (qRT-PCR), and the significant correlations among these key genes were identified. Notably, hsa-miR-17-3p, hsa-miR-3158-3p, hsa-miR-423-3p, and hsa-miR-193a-8p could regulate all key genes at the same time. In addition, Caffeine, Carboplatin, and Vopratelimab were the targeted drugs of these key genes. This study identified four platelet-related key genes of IS, which might help to deepen the understanding of the role of platelet-related genes in the molecular mechanism of IS.

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Section: Discussionmentioning

confidence: 99%

Analysis and Regulatory Mechanisms of Platelet-related Genes in Patients with Ischemic Stroke

Shu

et al. 2023

Preprint

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“…Protein extraction and western blotting were performed following a method as described earlier. 19 Briefly, cells were washed once with cold phosphate‐buffered saline (PBS) (Corning) and scraped into RIPA lysis buffer (Thermo Fischer Scientific) containing protease and phosphatase inhibitors. Cell lysates were sonicated and subsequently centrifuged at 13,400 g for 15 min at 4°C and supernatants were collected.…”

Section: Methodsmentioning

confidence: 99%

Profiling mitochondrial DNA mutations in tumors and circulating extracellular vesicles of triple‐negative breast cancer patients for potential biomarker development

Vikramdeo,

Anand,

Sudan

et al. 2023

FASEB BioAdvances

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Early detection and recurrence prediction are challenging in triple‐negative breast cancer (TNBC) patients. We aimed to develop mitochondrial DNA (mtDNA)‐based liquid biomarkers to improve TNBC management. Mitochondrial genome (MG) enrichment and next‐generation sequencing mapped the entire MG in 73 samples (64 tissues and 9 extracellular vesicles [EV] samples) from 32 metastatic TNBCs. We measured mtDNA and cardiolipin (CL) contents, NDUFB8, and SDHB protein expression in tumors and in corresponding circulating EVs. We identified 168 nonsynonymous mtDNA mutations, with 73% (123/186) coding and 27% (45/168) noncoding in nature. Twenty percent of mutations were nucleotide transversions. Respiratory complex I (RCI) was the key target, which harbored 44% (74/168) of the overall mtDNA mutations. A panel of 11 hotspot mtDNA mutations was identified among 19%–38% TNBCs, which were detectable in the serum‐derived EVs with 82% specificity. Overall, 38% of the metastatic tumor‐signature mtDNA mutations were traceable in the EVs. An appreciable number of mtDNA mutations were homoplasmic (18%, 31/168), novel (14%, 23/168), and potentially pathogenic (9%, 15/168). The overall and RCI‐specific mtDNA mutational load was higher in women with African compared to European ancestry accompanied by an exclusive abundance of respiratory complex (RC) protein NDUFB8 (RCI) and SDHB (RCII) therein. Increased mtDNA (p < 0.0001) content was recorded in both tumors and EVs along with an abundance of CL (p = 0.0001) content in the EVs. Aggressive tumor‐signature mtDNA mutation detection and measurement of mtDNA and CL contents in the EVs bear the potential to formulate noninvasive early detection and recurrence prediction strategies.

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“…MYB is generally highly expressed in most pancreatic cancer cells, irrespective of gene amplification, and is responsible for promoting their growth and malignant properties [ 66 ]. Recent work has identified the role of MYB in the hypoxic survival of the cancer cells, mediated by its ability to stimulate HIF1a expression and function [ 67 ]. In prostate cancer, MYB was also initially found to be amplified, especially in hormone-refractory cancer cases [ 68 ].…”

Section: The Role Of Myb In Human Cancermentioning

confidence: 99%

Transcription Factor MYB as Therapeutic Target: Current Developments

Klempnauer

2024

IJMS

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The MYB protein is a pivotal player in the cellular transcriptional network, influencing major important processes such as cell proliferation, differentiation, and apoptosis. Because of its role in oncogenesis, MYB is now a compelling target for therapeutic interventions in cancer research. This review summarizes its molecular functions and current therapeutic approaches aiming to inhibit its oncogenic activity.

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MYB sustains hypoxic survival of pancreatic cancer cells by facilitating metabolic reprogramming

Cited by 14 publications

References 74 publications

Analysis and Regulatory Mechanisms of Platelet-related Genes in Patients with Ischemic Stroke

Analysis and Regulatory Mechanisms of Platelet-related Genes in Patients with Ischemic Stroke

Profiling mitochondrial DNA mutations in tumors and circulating extracellular vesicles of triple‐negative breast cancer patients for potential biomarker development

Transcription Factor MYB as Therapeutic Target: Current Developments

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