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

Advanced Science, Journal Year: 2024, Volume and Issue: 11(40)

Published: July 19, 2024

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

Language: Английский

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Dual roles of human endogenous retroviruses in cancer progression and antitumor immune response

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(6), P. 189201 - 189201

Published: Oct. 18, 2024

Language: Английский

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Application of large-scale and multicohort plasma proteomics data to discover novel causal proteins in gastric cancer

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 18, 2024

Gastric cancer (GC) is one of the most common malignant tumors threatening human beings and has a poor prognosis. Therefore, exploring unveiled biomarkers or therapeutic targets for diagnosis treatment GC crucial. A total 5772 protein quantitative trait loci (pQTL) were aggregated from four latest large-scale proteomics cohorts. Two-sample Mendelian randomization (two-sample MR) was utilized to identify causal effect blood plasma proteins on GC. Heterogeneity, pleiotropy, directionality analyses employed evaluate identified via two-sample MR. The robustness results further validated colocalization. drug evaluated reveal compounds that can interfere with these proteins. Ten potential causations in relation identified: LY6D, SLURP1, MLN, PSCA, THSD1, CFTR, PPM1B, KDM3A, TSC1, HCG22. Among proteins, THSD1 considered as reliable due their significant H4 posterior probabilities colocalization analysis absence pleiotropy. Compound 35, nitrosamide, 0175029-0000 drugs small molecules targeting respectively. This study several provided data support new insights into early diagnosis, intervention,

Language: Английский

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Exploring Xiaojianzhong decoction's potential in gastric cancer treatment: Integrative insights and experimental validation

World Journal of Gastrointestinal Oncology, Journal Year: 2024, Volume and Issue: 16(12), P. 4553 - 4558

Published: Nov. 8, 2024

Gastric cancer (GC) remains a formidable global health concern with significant morbidity and mortality rates, despite the fact that numerous advances have been made to improve conventional therapies. Xiaojianzhong decoction (XJZ), traditional Chinese medicine, has garnered academic attention as multicomponent, multitarget approach managing GC. The present editorial explores potential of XJZ in treatment GC through comprehensive analysis network pharmacology experimental validation. Network was used identify key molecular targets XJZ, including interleukin 6, prostaglandin-endoperoxide synthase 2, matrix metalloproteinase 9,

Language: Английский

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