Dataset Information

DTL promotes melanoma progression through rewiring cell glucose metabolism.

ABSTRACT:

Background

To investigate the role of DTL in the development of skin cutaneous melanoma (SKCM) and possible mechanisms.

Methods

We examined the expression of DTL in SKCM in The Cancer Genome Atlas (TCGA) and Oncomine database and analyzed the relationship between DTL expression and melanoma prognosis. Furthermore, we silenced the DTL gene by RNA interference in A375 cells and investigated the effect of DTL silencing on the biological function of melanoma cells.

Results

The expression of DTL in SKCM was upregulated in the tumor tissues compared with the paired normal tissues. Survival analysis showed that higher DTL expression in SKCM patients was associated with poor clinical outcome compared with the lower DTL expression group. Silencing of DTL in A375 cells significantly inhibited the melanoma cell growth and proliferation ability, and also significantly decreased the total glucose consumption and lactate production. Gene set enrichment analysis (GSEA) showed that MYC targets gene set pathway was highly enriched in the DTL high expression group. The expression levels of some MYC targets-related oncogenes, including c-MYC, HK1, HK2, PGK1, ENO1, LDHA, IDH1, ACLY, and HMGCR, were reduced in the A375 cells with knockdown DTL and upregulated in SKCM tissues with high DTL expression, and there was a positive correlation between them.

Conclusions

An important role is played by DTL in promoting melanoma cell growth and glucose metabolism, possibly through activation of the MYC target pathway.

SUBMITTER: Lu JJ

PROVIDER: S-EPMC8848355 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

<i>DTL</i> promotes melanoma progression through rewiring cell glucose metabolism.

Lu Jia-Jing JJ Chen Fu-Juan FJ Li Ying Y Xu Xin X Peng Chen C Yu Ning N Su Li-Na LN Tang Li L

Annals of translational medicine 20220101 2

<h4>Background</h4>To investigate the role of <i>DTL</i> in the development of skin cutaneous melanoma (SKCM) and possible mechanisms.<h4>Methods</h4>We examined the expression of <i>DTL</i> in SKCM in The Cancer Genome Atlas (TCGA) and Oncomine database and analyzed the relationship between <i>DTL</i> expression and melanoma prognosis. Furthermore, we silenced the <i>DTL</i> gene by RNA interference in A375 cells and investigated the effect of <i>DTL</i> silencing on the biological function of ...[more]

PMID: 35282044

Similar Datasets

Project description:BackgroundUbiquitin E3 ligase CUL4A plays important oncogenic roles in the development of cancers. DTL, one of the CUL4-DDB1 associated factors (DCAFs), may involve in the process of cancer development. Programmed cell death 4 (PDCD4) is a tumor suppressor gene involved in cell apoptosis, transformation, invasion and tumor progression.MethodsAffinity-purification mass spectrometry was used to identify potential DTL interaction proteins. Co-immunoprecipitation (Co-IP) was performed to verify protein interaction between DTL and PDCD4. mRNA levels in cancer cells and tissues were detected by Quantitative real-time PCR. Lentivirus was used to establish stable overexpression and knocking down cell lines for DTL and PDCD4. Transwell and wound healing assays were used to determine migration ability of cancer cells. Matrigel assay was used to determine invasion ability of cancer cells. MTT and colony formation assays were used to evaluate proliferation of cancer cells.ResultsIn this study, programmed cell death 4 (PDCD4) was identified as a potential substrate of DTL. Co-IP and immunofluorescence assays further confirmed the interaction between DTL and PDCD4. Moreover, DTL overexpression decreased the protein level and accelerated the degradation rate of PDCD4. Through in vitro ubiquitination experiment, we proved that PDCD4 was degraded by DTL through ubiquitination. Clinically DTL was significantly up-regulated in cancer tissues than that in normal tissues. The survival curves showed that cancer patients with higher DTL expression owned lower survival rate. Functional experiments showed that DTL not only enhanced the proliferation and migration abilities of cancer cells, but also promoted the tumorigenesis in nude mice. Rescued experiment results demonstrated that silencing PDCD4 simultaneous with DTL recovered the phenotypes defect caused by DTL knocking down.ConclusionsOur results elucidated that DTL enhanced the motility and proliferation of cancer cells through degrading PDCD4 to promote the development of cancers.