HCP5 prevents ubiquitination-mediated UTP3 degradation to inhibit apoptosis by activating c-Myc transcriptional activity

Nan, Yabing; Luo, Qingyu; Wu, Xiaowei; Chang, Wan; Zhao, Pengfei; Shi, Liu; Liu, Zhihua

doi:10.1016/j.ymthe.2022.10.006

Cited by 15 publications

(8 citation statements)

References 49 publications

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“…1B-E). These results were consistent with the notion that failures in DNA repair, exceptional expression of MYC transcription factor family members, or abnormal assembly of oncogenic signaling hubs can trigger cell death [13][14][15][16] .…”

Section: Resultssupporting

confidence: 89%

Pan-cancer evaluation of regulated cell death to predict overall survival and immune checkpoint inhibitor response

Zhang,

Zhu,

Liu

et al. 2024

npj Precis. Onc.

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Regulated cell death (RCD) plays a pivotal role in various biological processes, including development, tissue homeostasis, and immune response. However, a comprehensive assessment of RCD status and its associated features at the pan-cancer level remains unexplored. Furthermore, despite significant advancements in immune checkpoint inhibitors (ICI), only a fraction of cancer patients currently benefit from treatments. Given the emerging evidence linking RCD and ICI efficacy, we hypothesize that the RCD status could serve as a promising biomarker for predicting the ICI response and overall survival (OS) in patients with malignant tumors. We defined the RCD levels as the RCD score, allowing us to delineate the RCD landscape across 30 cancer types, 29 normal tissues in bulk, and 2,573,921 cells from 82 scRNA-Seq datasets. By leveraging large-scale datasets, we aimed to establish the positive association of RCD with immunity and identify the RCD signature. Utilizing 7 machine-learning algorithms and 18 ICI cohorts, we developed an RCD signature (RCD.Sig) for predicting ICI response. Additionally, we employed 101 combinations of 10 machine-learning algorithms to construct a novel RCD survival-related signature (RCD.Sur.Sig) for predicting OS. Furthermore, we obtained CRISPR data to identify potential therapeutic targets. Our study presents an integrative framework for assessing RCD status and reveals a strong connection between RCD status and ICI effectiveness. Moreover, we establish two clinically applicable signatures and identify promising potential therapeutic targets for patients with tumors.

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Section: Resultssupporting

confidence: 89%

Pan-cancer evaluation of regulated cell death to predict overall survival and immune checkpoint inhibitor response

Zhang,

Zhu,

Liu

et al. 2024

npj Precis. Onc.

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show abstract

“…The autophagy is indeed a key mechanism by tumor cells to survive under stress including chemotherapy, and therefore representing a key target for cancer treatment [ 18 , 35 ]. Interestingly, VAMP3 has also been found to suppresses caspase-dependent apoptosis to enhance chemoresistance [ 36 ]. We observed that VAMP3 overexpression in the TNBC cells restored PTX resistance suppressed by CEBPD downregulation, along with the increased immunostaining of LC3.…”

Section: Discussionmentioning

confidence: 99%

CCAAT enhancer binding protein delta activates vesicle associated membrane protein 3 transcription to enhance chemoresistance and extracellular PD-L1 expression in triple-negative breast cancer

Zhao,

Yu,

et al. 2024

J Exp Clin Cancer Res

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Background Chemoresistance and immunosuppression are two major obstacles in the current anti-cancer treatments. This study investigates the involvements of a CCAAT enhancer binding protein delta (CEBPD)/vesicle associated membrane protein 3 (VAMP3) axis in paclitaxel (PTX) resistance and immune evasion in triple-negative breast cancer (TNBC). Methods PTX resistance-related genes were screened by bioinformatics. CEBPD and VAMP3 expression in clinical TNBC samples was examined by immunohistochemistry. Three PTX-resistant TNBC cell lines (MDA-MB-231/PTX, MDA-MB-468/PTX and MDA-MB-453/PTX) were generated, and their drug resistance was analyzed. Autophagy of cells was analyzed by immunofluorescence staining. Interaction between CEBPD and VAMP3 promoter was identified by immunoprecipitation and luciferase assays. The extracellular expression of programmed cell death-ligand 1 (PD-L1) in TNBC cells was detected. Extracellular vesicles (EVs) from TNBC cells were isolated to examine their effects on CD8+ T cell exhaustion. Results CEBPD and VAMP3 were upregulated in chemo-resistant tissue samples and in PTX-resistant TNBC cells. The CEBPD downregulation enhanced PTX sensitivity of cells. However, further upregulation of VAMP3 in cells restored PTX resistance, which was likely due to the activation of autophagy, as the autophagy antagonist chloroquine enhanced PTX sensitivity of cells. CEBPD was found to bind to the VAMP3 promoter to activate its transcription. The CEBPD/VAMP3 axis also increased the PD-L1 expression in the conditioned medium of TNBC cells. The TNBC cell-derived EVs increased the exhaustion of co-cultured CD8+ T cells. Conclusion This study provides novel evidence that CEBPD plays a key role in enhancing PTX resistance in TNBC cells across various subtypes through VAMP3-mediated autophagy activation. Additionally, the CEBPD/VAMP3 axis also increases extracellular PD-L1 level, delivered by cancer cell-derived EVs, to suppress CD8+ T cell-mediated anti-tumor immune response. These significant observations may provide new insights into the treatment of TNBC, suggesting CEBPD and VAMP3 as promising targets to overcome treatment resistance.

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“…For intratumoral GSDME knckdown experiment, AAV (AAV-shC or AAV-shGSDME) produced by ViGene Biosciences (Jinan, China) was intratumorally injected twice in 3-day intervals with 5.0 × 10 11 vg/mouse when the subcutaneous tumor becomes palpable 35 , 36 , 37 . Treatment was initiated when the tumors volume up to 100–120 mm 3 .…”

Section: Methodsmentioning

confidence: 99%

A high-throughput Gaussia luciferase reporter assay for screening potential gasdermin E activators against pancreatic cancer

Liu

Zhang

et al. 2023

Acta Pharmaceutica Sinica B

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HCP5 prevents ubiquitination-mediated UTP3 degradation to inhibit apoptosis by activating c-Myc transcriptional activity

Cited by 15 publications

References 49 publications

Pan-cancer evaluation of regulated cell death to predict overall survival and immune checkpoint inhibitor response

Pan-cancer evaluation of regulated cell death to predict overall survival and immune checkpoint inhibitor response

CCAAT enhancer binding protein delta activates vesicle associated membrane protein 3 transcription to enhance chemoresistance and extracellular PD-L1 expression in triple-negative breast cancer

A high-throughput Gaussia luciferase reporter assay for screening potential gasdermin E activators against pancreatic cancer

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