DTL promotes melanoma progression through rewiring cell glucose metabolism

Lu, Jiajing; Chen, Fujuan; Liu, Ying; Xu, Xin; Chen, Peng; Yu, Ning; Su, Li-Na; Tang, Li

doi:10.21037/atm-21-6648

Cited by 6 publications

(6 citation statements)

References 18 publications

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“… Yang et al (2019) suggested that DTL can be regarded as an indicator of poor prognosis in acral melanoma patients. DTL could play an important role in promoting melanoma cell growth and glucose metabolism, possibly through activation of the MYC target pathway ( Lu et al, 2022 ). In the present study, we found that overexpressed DTL was closely associated with worse survival outcomes in cutaneous melanoma patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of aberrantly methylated differentially expressed genes and pro-tumorigenic role of KIF2C in melanoma

Huang

Han

et al. 2022

Front. Genet.

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Background: Skin Cutaneous Melanoma (SKCM) is known as an aggressive malignant cancer, which could be directly derived from melanocytic nevi. However, the molecular mechanisms underlying the malignant transformation of melanocytes and melanoma tumor progression still remain unclear. Increasing research showed significant roles of epigenetic modifications, especially DNA methylation, in melanoma. This study focused on the identification and analysis of methylation-regulated differentially expressed genes (MeDEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles.Methods: The gene expression profiling datasets (GSE3189 and GSE114445) and gene methylation profiling datasets (GSE86355 and GSE120878) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified via GEO2R. MeDEGs were obtained by integrating the DEGs and DMGs. Then, a functional enrichment analysis of MeDEGs was performed. STRING and Cytoscape were used to describe the protein-protein interaction (PPI) network. Furthermore, survival analysis was implemented to select the prognostic hub genes. Next, we conducted gene set enrichment analysis (GSEA) of hub genes. To validate, SKCM cell culture and lentivirus infection was performed to reveal the expression and behavior pattern of KIF2C. Patients and specimens were collected and then immunohistochemistry (IHC) staining was conducted.Results: We identified 237 hypomethylated, upregulated genes and 182 hypermethylated, downregulated genes. Hypomethylation-upregulated genes were enriched in biological processes of the oxidation-reduction process, cell proliferation, cell division, phosphorylation, extracellular matrix disassembly and protein sumoylation. Pathway enrichment showed selenocompound metabolism, small cell lung cancer and lysosome. Hypermethylation-downregulated genes were enriched in biological processes of positive regulation of transcription from RNA polymerase II promoter, cell adhesion, cell proliferation, positive regulation of transcription, DNA-templated and angiogenesis. The most significantly enriched pathways involved the transcriptional misregulation in cancer, circadian rhythm, tight junction, protein digestion and absorption and Hippo signaling pathway. After PPI establishment and survival analysis, seven prognostic hub genes were CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2, and FBL. Moreover, the most involved hallmarks obtained by GSEA were E2F targets, G2M checkpoint and mitotic spindle. Importantly, among the 7 hub genes, we found that down-regulated level of KIF2C expression significantly inhibited the proliferative ability of SKCM cells and suppressed the metastasis capacity of SKCM cells.Conclusions: Our study identified potential aberrantly methylated-differentially expressed genes participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2, and FBL provided clues of aberrantly methylation-based biomarkers, which might improve the development of precision medicine. KIF2C plays a pro-tumorigenic role and potentially inhibited the proliferative ability in SKCM.

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Section: Discussionmentioning

confidence: 99%

Identification of aberrantly methylated differentially expressed genes and pro-tumorigenic role of KIF2C in melanoma

Huang

Han

et al. 2022

Front. Genet.

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“…As previously reports, overexpression of DTL has been found in many cancers and correlated with poor prognosis of cancer patients. In vitro experiments revealed that DTL overexpression promoted the proliferation, migration and invasion of cervical and breast cancer cell lines [ 15 , 25 ], while knockdown of DTL attenuated the growth of cancer cells [ 23 , 25 ]. Hence, the DTL gene might be a potential therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker

Tang

Gao

et al. 2023

BMC Cancer

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Background DTL has been found to be related with multiple cancers. However, comprehensive analyses, which identify the prediction value of DTL in diagnosis, prognosis, immune infiltration and treatment, have rarely been reported so far. Methods Combined with the data online databases, the gene expression, gene mutation, function enrichment and the correlations with the immunity status and clinical indexes of DTL were analyzed. Expression of DTL and the degree of immune cell infiltration were examined by immunofluorescence (IF) and immunohistochemistry (IHC) and analyzed by statistical analysis. Furthermore, the influences of DTL on the cell cycle, cell proliferation and apoptosis were detected by live cell imaging, IF and flow cytometric (FC) analysis. Genomic stability assays were conducted by chromosome slide preparation. Results DTL was widely expressed in various cells and tissues, while it was overexpressed in tumor tissues except acute myeloid leukemia (LAML). Pan-cancer bioinformatics analysis showed that the expression of DTL was correlated with the prognosis, immunotherapy, and clinical indexes in various cancers. In addition, gene set enrichment analysis (GSEA) uncovered that DTL was enriched in oocyte meiosis, pyrimidine metabolism, the cell cycle, the G2M checkpoint, mTORC1 signaling and E2F targets. Furthermore, the overexpression of DTL, and its association with immune cell infiltration and clinical indexes in liver hepatocellular carcinoma (LIHC), bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD) were verified in our study. It was also verified that overexpression of DTL could regulate the cell cycle, promote cell proliferation and cause genomic instability in cultured cells, which may be the reason why DTL plays a role in the occurrence, progression and treatment of cancer. Conclusions Collectively, this study suggested that DTL is of clinical value in the diagnosis, prognosis and treatment of various cancers, and may be a potential biomarker in certain cancers.

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“…GINS2 promoted cell proliferation, migration, invasion, and EMT via modulating PI3K/Akt and MEK/ERK signaling pathways [ 54 ], GINS2 knock-down stimulated inflammation and apoptosis in microglia [ 55 ]. DTL, a homolog of E3 ubiquitin ligase that belongs to the DCAF protein family, was reported to enhance the motility, proliferation, and invasion of cancer cells [ 56 , 57 ], and also significantly decrease total glucose consumption and lactate production [ 58 ]. ELANE, a factor that contributes to a protease-antiprotease imbalance and may cause inflammatory lung illnesses [ 59 ], induces autophagy, which in turn induces lung epithelial cell apoptosis and pulmonary emphysema through the overexpression of PGF [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of whole-transcriptome sequencing expression in COPD after personalized precise exercise training: a pilot study

Zhang

Gao

et al. 2023

Respir Res

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Background Chronic obstructive pulmonary disease (COPD) is one of the world’s leading causes of death and a major chronic respiratory disease. Aerobic exercise, the cornerstone of pulmonary rehabilitation, improves prognosis of COPD patients; however, few studies have comprehensively examined the changes in RNA transcript levels and the crosstalk between various transcripts in this context. This study identified the expression of RNA transcripts in COPD patients who engaged in aerobic exercise training for 12 weeks, and further constructions of the possible RNAs networks were made. Methods Peripheral blood samples for all four COPD patients who benefited from 12 weeks of PR were collected pre- and post-aerobic exercises and evaluated for the expression of mRNA, miRNA, lncRNA, and circRNA with high-throughput RNA sequencing followed by GEO date validation. In addition, enrichment analyses were conducted on different expressed mRNAs. LncRNA-mRNA and circRNA-mRNA coexpression networks, as well as lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA competing expression networks (ceRNAs) in COPD were constructed. Results We identified and analyzed the differentially expressed mRNAs and noncoding RNAs in the peripheral blood of COPD patients’ post-exercise. Eighty-six mRNAs, 570 lncRNAs, 8 miRNAs, and 2087 circRNAs were differentially expressed. Direct function enrichment analysis and Gene Set Variation Analysis showed that differentially expressed RNAs(DE-RNAs) correlated with several critical biological processes such as chemotaxis, DNA replication, anti-infection humoral response, oxidative phosphorylation, and immunometabolism, which might affect the progression of COPD. Some DE-RNAs were validated by Geo databases and RT-PCR, and the results were highly correlated with RNA sequencing. We constructed ceRNA networks of DE-RNAs in COPD. Conclusions The systematic understanding of the impact of aerobic exercise on COPD was achieved using transcriptomic profiling. This research offers a number of potential candidates for clarifying the regulatory mechanisms that exercise has on COPD, which could ultimately help in understanding the pathophysiology of COPD.

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DTL promotes melanoma progression through rewiring cell glucose metabolism

Cited by 6 publications

References 18 publications

Identification of aberrantly methylated differentially expressed genes and pro-tumorigenic role of KIF2C in melanoma

Identification of aberrantly methylated differentially expressed genes and pro-tumorigenic role of KIF2C in melanoma

Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker

Regulation of whole-transcriptome sequencing expression in COPD after personalized precise exercise training: a pilot study

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