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One bout of endurance exercise does not change gene expression or proliferation in a C26 colon carcinoma in immunocompetent mice

ABSTRACT: Purpose. Exercise typically reduces tumour growth, proliferation, and improves outcomes. Many of these effects require exercise to change gene expression within a tumour, but whether exercise affects gene expression within a tumour has not been investigated yet. The aim of this study was therefore to find out whether one bout of endurance exercise alters gene expression and proliferation in a C26 carcinoma in immunocompetent mice. Methods. BALB/c were injected with C26 colon carcinoma cells. Once the tumours had formed, the mice either ran for 65 min with increasing intensity or rested before the tumour was dissected. The tumours were then analysed by RNA-Seq and stained for the proliferation marker KI67. Results. One bout of running for 65 minutes did not systematically change gene expression in C26 carcinomas of BALB/c mice that ran for 65 minutes when compared to BALB/c mice that were rested. However, when analysed for sex, the RNA expression of 17, mostly skeletal muscle-related genes was higher in the samples of the female mice taken post exercise. Further histological analysis showed that this signal likely comes from the presence of muscle fibres from the panniculus carnosus muscle inside the tumours. Also, we found no differences in the positivity for the proliferation marker KI67 in the control and exercise C26 carcinomas. Conclusion. A bout of exercise did not systematically affect gene expression or proliferation in C26 carcinomas in immunocompetent BALB/c mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE244974 | GEO | 2023/10/15

REPOSITORIES: GEO

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Project description:We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA respons-es to one bout of lower-load (LL) versus higher-load (HL) resistance exercise. Trained col-lege-aged males (n=11, 23±4 years old, 4±3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 hours, and 6 hours after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina Methyl-ationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were sig-nificantly greater during the 30 Fail versus 80 Fail (p<0.001), although total training volume (sets x reps x load) was not significantly different between bouts (p=0.571). Regardless of bout, more CpG site methylation changes were observed at 3- versus 6-hours post exercise (239,951 versus 12,419, respectively; p<0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3- and 6-hours following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3- versus 6-hours following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 hours fol-lowing exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 hours following exercise (65% and 82%, respectively). While 30 Fail de-creased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar be-tween bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to “Focal adhesion”, “MAPK signaling”, and “PI3K-Akt signaling” were sig-nificantly affected at the 3- and 6-hour time points, and again this was regardless of bout. In con-clusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts.

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One bout of endurance exercise does not change gene expression or proliferation in a C26 colon carcinoma in immunocompetent mice

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