Dataset Information

HECTD3 promotes gastric cancer progression by mediating the polyubiquitination of c-MYC.

ABSTRACT: The E3 ubiquitin ligase HECTD3 is homologous with the E6 related protein carboxyl terminus, which plays a vital role in biological modification, including immunoreactivity, drug resistance and apoptosis. Current research indicates that HECTD3 promotes the malignant proliferation of multiple tumors and increases drug tolerance. Our study primarily explored the important function and effects of HECTD3 in gastric cancer. Here, we discovered that HECTD3 is abnormally activated in gastric cancer, and the clinical prognosis database suggested that HECTD3 was strongly expressed in gastric cancer. Depletion of HECTD3 restrained the proliferative and clone abilities of cells and induced the apoptosis of gastric cancer cells. Mechanistically, our findings revealed that interaction between HECTD3 and c-MYC, and that the DOC domain of HECTD3 interacted with the CP and bHLHZ domains of c-MYC. Furthermore, we discovered that HECTD3 mediates K29-linked polyubiquitination of c-MYC. Then, our research indicated that cysteine mutation at amino acid 823 (ubiquitinase active site) of HECTD3 reduces the polyubiquitination of c-MYC. Our experimental results reveal that HECTD3 facilitates the malignant proliferation of gastric cancer by mediating K29 site-linked polyubiquitination of c-MYC. HECTD3 might become a curative marker.

SUBMITTER: Zhang G

PROVIDER: S-EPMC8994759 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

HECTD3 promotes gastric cancer progression by mediating the polyubiquitination of c-MYC.

Zhang Guanghui G Zhu Qingzong Q Yan Xiaomin X Ci Mingxin M Zhao Erhu E Hou Jianbing J Wan Sicheng S Lü Muhan M Cui Hongjuan H

Cell death discovery 20220409 1

The E3 ubiquitin ligase HECTD3 is homologous with the E6 related protein carboxyl terminus, which plays a vital role in biological modification, including immunoreactivity, drug resistance and apoptosis. Current research indicates that HECTD3 promotes the malignant proliferation of multiple tumors and increases drug tolerance. Our study primarily explored the important function and effects of HECTD3 in gastric cancer. Here, we discovered that HECTD3 is abnormally activated in gastric cancer, and ...[more]

PMID: 35397617

Similar Datasets

Project description:The proto-oncogene c-Myc regulates multiple biological processes mainly through selectively activating gene expression. However, the mechanisms underlying c-Myc-mediated gene repression in the context of cancer remain less clear. This study aimed to clarify the role of PRMT5 in the transcriptional repression of c-Myc target genes in gastric cancer. Methods: Immunohistochemistry was used to evaluate the expression of PRMT5, c-Myc and target genes in gastric cancer patients. PRMT5 and c-Myc interaction was assessed by immunofluorescence, co-immunoprecipitation and GST pull-down assays. Bioinformatics analysis, immunoblotting, real-time PCR, chromatin immunoprecipitation, and rescue experiments were used to evaluate the mechanism. Results: We found that c-Myc directly interacts with protein arginine methyltransferase 5 (PRMT5) to transcriptionally repress the expression of a cohort of genes, including PTEN, CDKN2C (p18INK4C), CDKN1A (p21CIP1/WAF1), CDKN1C (p57KIP2) and p63, to promote gastric cancer cell growth. Specifically, we found that PRMT5 was required to promote gastric cancer cell growth in vitro and in vivo, and for transcriptional repression of this cohort of genes, which was dependent on its methyltransferase activity. Consistently, the promoters of this gene cohort were enriched for both PRMT5-mediated symmetric di-methylation of histone H4 on Arg 3 (H4R3me2s) and c-Myc, and c-Myc depletion also upregulated their expression. H4R3me2s also colocalized with the c-Myc-binding E-box motif (CANNTG) on these genes. We show that PRMT5 directly binds to c-Myc, and this binding is required for transcriptional repression of the target genes. Both c-Myc and PRMT5 expression levels were upregulated in primary human gastric cancer tissues, and their expression levels inversely correlated with clinical outcomes. Conclusions: Taken together, our study reveals a novel mechanism by which PRMT5-dependent transcriptional repression of c-Myc target genes is required for gastric cancer progression, and provides a potential new strategy for therapeutic targeting of gastric cancer.

Dataset Information

HECTD3 promotes gastric cancer progression by mediating the polyubiquitination of c-MYC.

Publications

HECTD3 promotes gastric cancer progression by mediating the polyubiquitination of c-MYC.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets