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MiR-22 gene therapy as a novel option for HCC treatment in part via augmentation of retinoic acid but silencing IL17 signaling in orthotopic murine models

ABSTRACT: miR-22 gene therapy as a novel option for HCC treatment in part via augmentation of retinoic acid but silencing IL17 signaling in orthotopic murine models

PROVIDER: PRJNA890563 | ENA |

REPOSITORIES: ENA

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miR-22 gene therapy as a novel option for HCC treatment in part via augmentation of retinoic acid but silencing IL17 signaling in orthotopic murine models

Project description:miR-22 expression is reduced in hepatocellular carcinoma (HCC), a deadly cancer with very limited treatment options. Our published data showed that retinoic acid (RA) via its receptor RARβ induces miR-22. Moreover, miR-22 increase the expression of RARβ, which signifies the significance of RA signaling in tumor suppression. Using orthotopic HCC mice models including β-catenin positive HCC, we studied the anti-HCC effect of miR-22 for the first time focusing on the potential roles of RA signaling in regulating tumor immunity based on transcriptomic profiling data found in both mouse and human HCC. Our data showed that miR-22 treated HCC without toxicity, with improved survival compared with Lenvatinib. Reduced RA signaling and increased IL17 signaling found in mouse HCC as well as isolated T cells were consistently found in miR-22 low human HCC, whereas miR-22 treatment of mouse HCC reversed both pathways verified in β-catenin positive HCC. Moreover, in isolated T cells, miR-22 silenced the Il17a gene, which lead to Th17 cell reduction, by reducing the recruitment of HIFα to the Rorc gene as well as the RORγT, HIF1α, and STAT3 to the Il17a gene. Further, IL23-driven IL17 signaling expansion attenuated the anti-HCC effects of miR-22. Additionally, CD8 blockade diminished the therapeutic effects of miR-22. Together, via regulating tumor immunity, miR-22 can be a novel option for HCC treatment.

2023-08-21 | GSE215753 | GEO

Analysis of the function of IL17 in C.elegans

Project description:RNAseq of C.elegans mutants of varying IL17 loss and gain of function mutants

2022-07-08 | E-MTAB-11701 | biostudies-arrayexpress

Single cell transcriptomics profiling of vessel co-option

Project description:Vessel co-option is an alternative mode of tumor vascularization, which contributes to resistance to anti-angiogenic therapy (AAT). In contrast to vessel sprouting (angiogenesis), knowledge about the mechanisms underlying vessel co-option is minimal, precluding therapeutic strategies. We therefore single-cell RNA-sequenced 31,964 cells from a murine lung metastasis model with vessel co-option, characterized by resistance to AAT. Unexpectedly, co-opted endothelial cells (ECs) were transcriptomically indistinguishable from healthy ECs and lacked an activation signature, while co-opted pericytes expressed a quiescence signature, in contrast to activated pericytes during angiogenesis. Compared with cancer cells during angiogenesis, co-opting cancer cells were phenotypically more diverse and enriched in invasive subpopulations. Together, these data reveal new insight into vessel co-option, with possible implications for the development of therapeutic targets.

2021-06-15 | E-MTAB-9227 | biostudies-arrayexpress

Transcription profiling of human T84 colonic epithelial cell line response to IL17 and IL22 stimulation

Project description:The effects of stimulating intestinal epithelial cells with Th17 cytokines, IL17 and IL22, was investigated Experiment Overall Design: The human colonic epithelial cell line, T84 was grown to confluency in standard transwell plates and either mock treated, or treated with cytokines IL17 and IL22

2008-06-20 | E-GEOD-11345 | biostudies-arrayexpress

Transcriptome profile of NON CF (normal) bronchial epithelial cells treated with TNFalpha, IL17 and TNFalpha+IL17

Project description:To analyse gene expression differences between differentiated bronchial epithelial cells kept under control conditions or treated for 72 hours with cytokines (TNFalpha10 ng/ml; IL17 20ng/ml)

2022-10-19 | GSE182957 | GEO

IL17 and IL22 stimulation of T84 colonic epithelial cell line

Project description:The effects of stimulating intestinal epithelial cells with Th17 cytokines, IL17 and IL22, was investigated Keywords: dose response

2008-05-07 | GSE11345 | GEO

anti-IL17 in RA

Project description:RNAseq of biopsies of RA patients treated with anti-IL17

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Glioblastoma Orthotopic Xenograft Transcriptome

Project description:Transcriptional profiling of glioblastoma orthotopic xenografts Descriptive experiment, comparison of 39 glioblastoma tumors as orthotopic xenografts

2012-07-10 | E-GEOD-38814 | biostudies-arrayexpress

Transcriptome profile of NON CF (normal) bronchial epithelial cells treated with TNFalpha, IL17 and TNFalpha+IL17

Project description:Transcriptome profile of NON CF (normal) bronchial epithelial cells treated with TNFalpha, IL17 and TNFalpha+IL17

| PRJNA758426 | ENA

Characterization of the IL23-IL17 immune axis in IBD patients

Project description:The aim of this study is to investigate the molecular mechanisms of IL23-IL17 immune axis in IBD, with particular attention to its role in maintaining mucosal barrier integrity under both physiological and pathological conditions

2021-11-26 | GSE165512 | GEO

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