Posters

Presenting Author

Swati Dhasmana

Presenting Author Academic/Professional Position

Post-doc

Academic Level (Author 1)

Post-doc

Discipline/Specialty (Author 1)

Immunology and Microbiology

Academic Level (Author 2)

Faculty

Discipline/Specialty (Author 2)

Immunology and Microbiology

Discipline/Specialty (Author 3)

Immunology and Microbiology

Academic Level (Author 4)

Faculty

Discipline/Specialty (Author 4)

Immunology and Microbiology

Academic Level (Author 5)

Faculty

Discipline/Specialty (Author 5)

Immunology and Microbiology

Presentation Type

Poster

Discipline Track

Biomedical Science

Abstract Type

Research/Clinical

Abstract

Background: MUC13 has emerged as a potent oncoprotein and gained considerable attention. The overexpression or aberrant expression of MUC13 is strongly linked to cancer progression, and poor clinical outcomes in multiple malignancies, including colorectal cancer (CRC), however its precise mechanisms are not fully unfolded. Towards this, we have generated a MUC13 transgenic mice model and in this research, we have investigated the effect of transgenic MUC13 overexpression on gut microbiome, gut histology, and cytokine expression profile as recent studies have shown critical role of microbiome in cancer progression and cancer therapeutics.

Methods: In this study we sought to decipher the association between differential gut microbiota and chemokine/cytokine expression in MUC13 overexpressed mice vs Wild Type mice. Comparative profiling of bacterial populations in fecal samples of MUC13 overexpressed C57BL6 mice vs Wild Type C57BL6 mice were analyzed using 16S rRNA-based metagenomics using Illumina Miseq. DNA was extracted using Qiagen DNeasy PowerSoil Pro Kit. The quantity and quality of the DNA were assessed using a NanoDrop 2000 spectrophotometer and a Qubit dsDNA Broad-Range assay. The bioinformatic analyses were performed using Mothur tool on Galaxy server to obtain OTUs (Operational Taxonomic Units) clustering for taxonomic profiling, while community structure and taxonomic classification were determined by Phinch tool and Krona pie charts, respectively. The phyla and species abundance plots were generated using Phyloseq R platform. In addition to gut microbiota, the effect of transgenic MUC13 expression on 111 key cancer associated chemokines/cytokines in serum samples was evaluated using the ‘Proteome Profiler Mouse XL Cytokine Array’ (RnD Systems: ARY028).

Results: The Phinch tool displayed OTU (spell it out) counts suggest differential abundance of some specific genera such as Xylanibacter and Oscillibacter in the fecal samples of MUC13 Tg mice as compared to wild type (WT). This study revealed significant decrease (Alistipes, Clostridium_XIVa, Oscillibacter, and TM7 29 to 21, 8 to 2, 13 to 9, 5 to 2%, respectively) and increase (Parabacteroides, Akkermansia, Rikenellaceae, 21 to 30, 3 to 9, 10-14%, respectively) in bacterial population among MUC13Tg versus wild type mice. The chemokine/cytokine array results suggest upregulation of EGF, FGF21, CD93, Leptin in the MUC13 Tg mice, while 11 cytokines shown downregulation (Angiopoietin-1, CD14, HGF, CCL17, TIG-2, MCSF, CCL22, CX3CL1, PTX3, FIZZ3, Thrombopoietin) in the MUC13 Tg mice as compared to the wild type mice.

Conclusion: This study for the first time revealed that the transgenic overexpression of MUC13 can significantly alter the gut microbiome and cytokine expression profile in C57BL6 mice. These results suggest a potential link between MUC13 expression and gut microbiome. These findings also suggest that the overexpression of MUC13 might impact both gut microbiota composition and immune responses that can potentially influence oncogenic mechanisms and colorectal cancer progression.

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Transgenic MUC13 overexpression influenced gut microbiota and chemokines expression profile in mice

Background: MUC13 has emerged as a potent oncoprotein and gained considerable attention. The overexpression or aberrant expression of MUC13 is strongly linked to cancer progression, and poor clinical outcomes in multiple malignancies, including colorectal cancer (CRC), however its precise mechanisms are not fully unfolded. Towards this, we have generated a MUC13 transgenic mice model and in this research, we have investigated the effect of transgenic MUC13 overexpression on gut microbiome, gut histology, and cytokine expression profile as recent studies have shown critical role of microbiome in cancer progression and cancer therapeutics.

Methods: In this study we sought to decipher the association between differential gut microbiota and chemokine/cytokine expression in MUC13 overexpressed mice vs Wild Type mice. Comparative profiling of bacterial populations in fecal samples of MUC13 overexpressed C57BL6 mice vs Wild Type C57BL6 mice were analyzed using 16S rRNA-based metagenomics using Illumina Miseq. DNA was extracted using Qiagen DNeasy PowerSoil Pro Kit. The quantity and quality of the DNA were assessed using a NanoDrop 2000 spectrophotometer and a Qubit dsDNA Broad-Range assay. The bioinformatic analyses were performed using Mothur tool on Galaxy server to obtain OTUs (Operational Taxonomic Units) clustering for taxonomic profiling, while community structure and taxonomic classification were determined by Phinch tool and Krona pie charts, respectively. The phyla and species abundance plots were generated using Phyloseq R platform. In addition to gut microbiota, the effect of transgenic MUC13 expression on 111 key cancer associated chemokines/cytokines in serum samples was evaluated using the ‘Proteome Profiler Mouse XL Cytokine Array’ (RnD Systems: ARY028).

Results: The Phinch tool displayed OTU (spell it out) counts suggest differential abundance of some specific genera such as Xylanibacter and Oscillibacter in the fecal samples of MUC13 Tg mice as compared to wild type (WT). This study revealed significant decrease (Alistipes, Clostridium_XIVa, Oscillibacter, and TM7 29 to 21, 8 to 2, 13 to 9, 5 to 2%, respectively) and increase (Parabacteroides, Akkermansia, Rikenellaceae, 21 to 30, 3 to 9, 10-14%, respectively) in bacterial population among MUC13Tg versus wild type mice. The chemokine/cytokine array results suggest upregulation of EGF, FGF21, CD93, Leptin in the MUC13 Tg mice, while 11 cytokines shown downregulation (Angiopoietin-1, CD14, HGF, CCL17, TIG-2, MCSF, CCL22, CX3CL1, PTX3, FIZZ3, Thrombopoietin) in the MUC13 Tg mice as compared to the wild type mice.

Conclusion: This study for the first time revealed that the transgenic overexpression of MUC13 can significantly alter the gut microbiome and cytokine expression profile in C57BL6 mice. These results suggest a potential link between MUC13 expression and gut microbiome. These findings also suggest that the overexpression of MUC13 might impact both gut microbiota composition and immune responses that can potentially influence oncogenic mechanisms and colorectal cancer progression.

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