ARID1A loss derepresses a group of human endogenous retrovirus-H loci to modulate BRD4-dependent transcription

Yu, Chunhong; Lei, Xianfu; Chen, Fang; Mao, Song; Lv, Lu; Liu, Honglu; Hu, Xiaofang; Wang, Runhan; Shen, Licong; Zhang, Na; Meng, Yunxiao; Shen, Yidong; Chen, Jiale; Li, Pishun; Huang, Shi; Lin, Changwei; Zhang, Zhuohua; Yuan, Kai

doi:10.1038/s41467-022-31197-4

Cited by 15 publications

(13 citation statements)

References 97 publications

(123 reference statements)

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“…Heatmaps were created using R package pheatmap v1.0.12. The GO enrichment analysis was performed using the function "enrichGO" from the R package clusterProfiler v3.10.188 79 .…”

Section: Rna-seq and Bioinformatic Analysismentioning

confidence: 99%

Impairment of FBXO31-mediated Ubiquitination of OGT Upregulates O-GlcNAcylation to Advance Endometrial Malignancy

Yuan,

Zhang,

Meng

et al. 2024

Preprint

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Aberrant O-GlcNAc cycling of the cancer proteome is a manifestation of its metabolic plasticity. As one of the most common cancer of the female genital tract associated with metabolic syndrome, endometrial cancer (EC) tissues often bear altered O-GlcNAcylation patterns. However, integration of O-GlcNAc status with existing histomorphologic and molecular subtypes of EC in large cohorts and identification of molecular modules controlling the O-GlcNAc homeostasis remain to be accomplished. Here we establish a positive correlation of O-GlcNAcylation with histologic grade of EC in a Chinese cohort containing 219 tumors and consolidate it in The Cancer Genome Atlas (TCGA) EC dataset. Higher O-GlcNAc level is associated with less pathological differentiation and poorer prognosis. Functionally, increasing O-GlcNAcylation promotes proliferation and stem-like cell properties in normal endometrial epithelial organoids (EE-Os), whereas decreasing O-GlcNAcylation limits the growth of endometrial cancer organoids (EC-Os). Using genome-wide CRISPR screen, we further identify that the F-box only protein 31 (FBXO31), whose loss of heterozygosity is frequently observed in cancer, regulates O-GlcNAc homeostasis. FBXO31 acts as a substrate receptor of the SCF ubiquitin ligase complex to ubiquitinate the O-GlcNAc transferase OGT. Loss of FBXO31 results in accumulation of OGT and upregulation of O-GlcNAcylation in EC. Our study highlights the O-GlcNAcylation as a useful stratification marker and potential therapeutic target for the advanced, poorly differentiated EC cases.

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“…Heatmaps were created using R package pheatmap v1.0.12. The GO enrichment analysis was performed using the function "enrichGO" from the R package clusterProfiler v3.10.188 79 .…”

Section: Rna-seq and Bioinformatic Analysismentioning

confidence: 99%

Impairment of FBXO31-mediated Ubiquitination of OGT Upregulates O-GlcNAcylation to Advance Endometrial Malignancy

Yuan,

Zhang,

Meng

et al. 2024

Preprint

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“…For patients who are not sensitive to chemoradiotherapy, PDTOs can not only help find new therapeutic targets, but also conduct basic research. Yu et al 118 found that inhibition of human specific endogenous retrovirus H prevented the growth of colon cancer cells and PDTOs. It has been demonstrated that fibrillin-1/vascular endothelial growth factor-2/ signal transducer and activator of transcription 2 signaling pathway can induce chemotherapy resistance in ovarian PDTOs by participating in glycolysis and angiogenesis 33 .…”

Section: Application Of Tumor Organoid Biobanksmentioning

confidence: 99%

Tumor organoid biobank-new platform for medical research

Song

2023

Sci Rep

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Organoids are a new type of 3D model for tumor research, which makes up for the shortcomings of cell lines and xenograft models, and promotes the development of personalized precision medicine. Long-term culture, expansion and storage of organoids provide the necessary conditions for the establishment of biobanks. Biobanks standardize the collection and preservation of normal or pathological specimens, as well as related clinical information. The tumor organoid biobank has a good quality control system, which is conducive to the clinical transformation and large-scale application of tumor organoids, such as disease modeling, new drug development and high-throughput drug screening. This article summarized the common tumor types of patient-derived organoid (PDO) biobanks and the necessary information for biobank construction, such as the number of organoids, morphology, success rate of culture and resuscitation, pathological types. In our results, we found that patient-derived tumor organoid (PDTO) biobanks were being established more and more, with the Netherlands, the United States, and China establishing the most. Biobanks of colorectal, pancreas, breast, glioma, and bladder cancers were established more, which reflected the relative maturity of culture techniques for these tumors. In addition, we provided insights on the precautions and future development direction of PDTO biobank building.

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“…And the antiviral drugs down-regulated HERV gene expression, combined with anticancer drugs may have a synergistic antitumor effect, especially in chemorefractory tumors, which has therapeutic significance for CRC patients ( Díaz-Carballo et al, 2015 ). HERV-H was transcriptionally upregulated in colorectal cancer tissue and was associated with mutations in several tumor suppressors, including ARID1A ( Yu et al, 2022 ). In addition, the knockout of the HERV-K env affected the cell proliferation, migration, and tumor colony formation abilities of colorectal cancer cells through nupr1-related pathways ( Ko et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…These results suggested a possible link between HERV and colorectal cancer. Most current studies above have focused on the expression of some elements of other HERV families and the HERV-K (HML-2) gene in colorectal cancer ( Golkaram et al, 2021 ; Steiner et al, 2021 ; Yu et al, 2022 ). The relationship between HERV-K(HML-2) expressed in the blood of colorectal cancer lacks a more comprehensive description.…”

Section: Introductionmentioning

confidence: 99%

Identification of differentially expressed HERV-K(HML-2) loci in colorectal cancer

Kang

Guo

et al. 2023

Front. Microbiol.

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Colorectal cancer is one of the malignant tumors with the highest mortality rate in the world. Survival rates vary significantly among patients at various stages of the disease. A biomarker capable of early diagnosis is required to facilitate the early detection and treatment of colorectal cancer. Human endogenous retroviruses (HERVs) are abnormally expressed in various diseases, including cancer, and have been involved in cancer development. Real-time quantitative PCR was used to detect the transcript levels of HERV-K(HML-2) gag, pol, and env in colorectal cancer to systematically investigate the connection between HERV-K(HML-2) and colorectal cancer. The results showed that HERV-K(HML-2) transcript expression was significantly higher than healthy controls and was consistent at the population and cell levels. We also used next-generation sequencing to identify and characterize HERV-K(HML-2) loci that were differentially expressed between colorectal cancer patients and healthy individuals. The analysis revealed that these loci were concentrated in immune response signaling pathways, implying that HERV-K impacts the tumor-associated immune response. Our results indicated that HERV-K might serve as a screening tumor marker and a target for tumor immunotherapy in colorectal cancer.

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ARID1A loss derepresses a group of human endogenous retrovirus-H loci to modulate BRD4-dependent transcription

Cited by 15 publications

References 97 publications

Impairment of FBXO31-mediated Ubiquitination of OGT Upregulates O-GlcNAcylation to Advance Endometrial Malignancy

Impairment of FBXO31-mediated Ubiquitination of OGT Upregulates O-GlcNAcylation to Advance Endometrial Malignancy

Tumor organoid biobank-new platform for medical research

Identification of differentially expressed HERV-K(HML-2) loci in colorectal cancer

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