Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer

Wang, Jinghan; Ren, Mindong; Yu, Jundan; Hu, Mingtai; Wang, Xiaojing; Ma, Wencong; Jiang, Xiaoqing; Cui, Jie

doi:10.1016/j.ebiom.2022.104319

Cited by 17 publications

(14 citation statements)

References 72 publications

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“…Out of the 210 genes, 153 have either a TE GeneHancer or TE ENCODE cCREs interaction, providing further support to the hypothesis of TEs playing a regulatory role in GC. The remaining interactions met the correlation threshold, and the gene is in close genomic vicinity of the TEs, consistent with previous findings 13,35 suggesting such a regulatory role for TEs.…”

Section: Resultssupporting

confidence: 90%

“…Notably, there are 2 milestones with a high number of IMS cells, with one of them continuing directly to the Cancer milestone. To add support to the trajectory in the context of cancer evolution, I also applied inferCNV 41 to generate per-cell scores of copy number variations (CNVs), which has been used as proxy of malignancy development 13 . The inferCNV scores projected in the trajectory are also in concordance with the progression of CAG to IM, and subsequently to EGC ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To ask about the potential role of TEs as regulators of gene expression, a methodology similar to previous works 13,43 was applied: (1) using all the locus-specific TEs detected in both the single-cell and the spatial analysis, a gene-TE dictionary was built, considering all genes within 500 kbp of each TE; (2) Afterwards, to characterize the regulatory potential of TEs, the overlap with regulatory elements in GeneHancer and the ENCODE SCREEN candidate Cis-Regulatory Elements (cCREs) was assessed; (3) the gene-TE dictionary was filtered by considering either pre-defined interactions in GeneHancer or SCREEN, or if the gene was within 50 kbp of the TE; (4) finally, the Spearman correlation values were calculated for each gene-TE pair, and all interactions with correlation ≥ 0.3 were kept.…”

Section: Resultsmentioning

confidence: 99%

“…Although this has allowed for many advances in our knowledge, it has been somewhat limited for studying cancer due to intratumor heterogeneity 12 . In turn, recent works using higher-resolution modalities of RNA-Seq, such as single-cell (scRNA-Seq) and spatially-resolved (srRNA-Seq), have been published 6,13,14 . In addition to the identification of tumor subpopulations, scRNA-Seq allows for the reconstruction of cell trajectories through Trajectory Inference (TI) methods.…”

Section: Introductionmentioning

confidence: 99%

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The spatial and cellular portrait of Transposable Element expression during Gastric Cancer

Valdebenito-Maturana

2024

Preprint

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Gastric Cancer (GC) is a lethal malignancy, with urgent need for the discovery of novel biomarkers for its early detection. I previously showed that Transposable Elements (TEs) become activated in early GC (EGC), suggesting a role in gene expression. Here, I follow-up on that evidence using single-cell data from gastritis to EGC, and show that TEs are expressed and follow the disease progression, with 2,430 of them being cell populations markers. Pseudotemporal trajectory modeling revealed 111 TEs associated with the origination of cancer cells. Analysis of spatial data from GC also confirms TE expression, with 204 TEs being spatially enriched. Finally, a network of TE-mediated gene regulation was modeled, indicating that ~2,000 genes could be modulated by TEs, with ~500 of them already implicated in cancer. These results suggest that TEs might play a functional role in GC progression, and highlights them as potential biomarker for its early detection.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The spatial and cellular portrait of Transposable Element expression during Gastric Cancer

Valdebenito-Maturana

2024

Preprint

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“…[2,11,12] Furthermore, co-infection with GB virus C (GBV-C) is associated with a better prognosis in people living with HIV (PLWH) and activation of the human endogenous retroviruses (HERV) could serve as a potential early diagnostic biomarker for gallbladder cancer. [13][14][15] These studies emphasized the significance of exploring the virome in conditions of immunodeficiency diseases. Hence, conducting virome studies within the immunodeficiency community can potentially uncover essential links between changes in specific virome components and compromised immunity.…”

Section: Introductionmentioning

confidence: 99%

Virome in immunodeficiency: what we know currently

Wang,

Xu,

et al. 2023

Chinese Medical Journal

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Over the past few years, the human virome and its' complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health. Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases. This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status. By surveying the latest literature, we present a detailed overview of virome alterations observed in various immunodeficiency conditions. We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals. Furthermore, this review explores the clinical relevance of virome studies in the context of immunodeficiency, highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.

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KDM3A Ablation Activates Endogenous Retrovirus Expression to Stimulate Antitumor Immunity in Gastric Cancer

Zheng,

Feng,

Lin

et al. 2024

Advanced Science

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The success of immunotherapy for cancer treatment is limited by the presence of an immunosuppressive tumor microenvironment (TME); Therefore, identifying novel targets to that can reverse this immunosuppressive TME and enhance immunotherapy efficacy is essential. In this study, enrichment analysis based on publicly available single‐cell and bulk RNA sequencing data from gastric cancer patients are conducted, and found that tumor‐intrinsic interferon (IFN) plays a central role in TME regulation. The results shows that KDM3A over‐expression suppresses the tumor‐intrinsic IFN response and inhibits KDM3A, either genomically or pharmacologically, which effectively promotes IFN responses by activating endogenous retroviruses (ERVs). KDM3A ablation reconfigures the dsRNA‐MAVS‐IFN axis by modulating H3K4me2, enhancing the infiltration and function of CD8 T cells, and simultaneously reducing the presence of regulatory T cells, resulting in a reshaped TME in vivo. In addition, combining anti‐PD1 therapy with KDM3A inhibition effectively inhibited tumor growth. In conclusions, this study highlights KDM3A as a potential target for TME remodeling and the enhancement of antitumor immunity in gastric cancer through the regulation of the ERV‐MAVS‐IFN axis.

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Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer

Cited by 17 publications

References 72 publications

The spatial and cellular portrait of Transposable Element expression during Gastric Cancer

The spatial and cellular portrait of Transposable Element expression during Gastric Cancer

Virome in immunodeficiency: what we know currently

KDM3A Ablation Activates Endogenous Retrovirus Expression to Stimulate Antitumor Immunity in Gastric Cancer

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