High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor Suppressors

High-intensity aerobic exercise (90% of the maximal heart rate) can effectively suppress cancer cell proliferation in vivo. However, the molecular effects of exercise and its relevance to cancer prevention remain uninvestigated. In this study, mice with colorectal cancer were subjected to high-inten...

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Main Authors: Hyunseok Jee, Eunmi Park, Kyunghoon Hur, Minjeong Kang, Yoosik Kim
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2022.818470/full
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author Hyunseok Jee
Hyunseok Jee
Eunmi Park
Kyunghoon Hur
Minjeong Kang
Yoosik Kim
Yoosik Kim
author_facet Hyunseok Jee
Hyunseok Jee
Eunmi Park
Kyunghoon Hur
Minjeong Kang
Yoosik Kim
Yoosik Kim
author_sort Hyunseok Jee
collection DOAJ
description High-intensity aerobic exercise (90% of the maximal heart rate) can effectively suppress cancer cell proliferation in vivo. However, the molecular effects of exercise and its relevance to cancer prevention remain uninvestigated. In this study, mice with colorectal cancer were subjected to high-intensity aerobic exercise, and mRNA-seq analysis was performed on the heart, lungs, and skeletal muscle tissues to analyze the genome-wide molecular effects of exercise. The skeletal muscle-derived genes with exercise-dependent differential expression were further evaluated for their effects on colorectal cancer cell viability. Compared to the results obtained for the control groups (healthy and cancer with no exercise), the regular and high-intensity aerobic physical activity in the mice produced positive results in comprehensive parameters (i.e., food intake, weight gain, and survival rate). A heatmap of differentially expressed genes revealed markedly different gene expression patterns among the groups. RNA-seq analysis of 23,282 genes expressed in the skeletal muscle yielded several anticancer effector genes (e.g., Trim63, Fos, Col1a1, and Six2). Knockdown and overexpression of selected anticancer genes repressed CT26 murine colorectal carcinoma cell proliferation by 20% (p < 0.05). Our findings, based on the aerobic exercise cancer mouse model, suggest that high-intensity aerobic exercise results in a comprehensive change in the expression patterns of genes, particularly those that can affect cancer cell viability. Such an approach may identify key exercise-regulated genes that can help the body combat cancer.
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spelling doaj.art-dad9161a9ec3413d8f46c3817cc43b522022-12-22T03:30:52ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-06-01910.3389/fmolb.2022.818470818470High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor SuppressorsHyunseok Jee0Hyunseok Jee1Eunmi Park2Kyunghoon Hur3Minjeong Kang4Yoosik Kim5Yoosik Kim6School of Kinesiology, Yeungnam University, Gyeongsan, South KoreaCollege of Life Science and Nano Technology, Hannam University, Daejeon, South KoreaCollege of Life Science and Nano Technology, Hannam University, Daejeon, South KoreaDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South KoreaDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South KoreaDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South KoreaKAIST Institute for Health Science and Technology (KIHST), KAIST, Daejeon, South KoreaHigh-intensity aerobic exercise (90% of the maximal heart rate) can effectively suppress cancer cell proliferation in vivo. However, the molecular effects of exercise and its relevance to cancer prevention remain uninvestigated. In this study, mice with colorectal cancer were subjected to high-intensity aerobic exercise, and mRNA-seq analysis was performed on the heart, lungs, and skeletal muscle tissues to analyze the genome-wide molecular effects of exercise. The skeletal muscle-derived genes with exercise-dependent differential expression were further evaluated for their effects on colorectal cancer cell viability. Compared to the results obtained for the control groups (healthy and cancer with no exercise), the regular and high-intensity aerobic physical activity in the mice produced positive results in comprehensive parameters (i.e., food intake, weight gain, and survival rate). A heatmap of differentially expressed genes revealed markedly different gene expression patterns among the groups. RNA-seq analysis of 23,282 genes expressed in the skeletal muscle yielded several anticancer effector genes (e.g., Trim63, Fos, Col1a1, and Six2). Knockdown and overexpression of selected anticancer genes repressed CT26 murine colorectal carcinoma cell proliferation by 20% (p < 0.05). Our findings, based on the aerobic exercise cancer mouse model, suggest that high-intensity aerobic exercise results in a comprehensive change in the expression patterns of genes, particularly those that can affect cancer cell viability. Such an approach may identify key exercise-regulated genes that can help the body combat cancer.https://www.frontiersin.org/articles/10.3389/fmolb.2022.818470/fullexercisecancerRNA-seqskeletal muscletumor suppressors
spellingShingle Hyunseok Jee
Hyunseok Jee
Eunmi Park
Kyunghoon Hur
Minjeong Kang
Yoosik Kim
Yoosik Kim
High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor Suppressors
Frontiers in Molecular Biosciences
exercise
cancer
RNA-seq
skeletal muscle
tumor suppressors
title High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor Suppressors
title_full High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor Suppressors
title_fullStr High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor Suppressors
title_full_unstemmed High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor Suppressors
title_short High-Intensity Aerobic Exercise Suppresses Cancer Growth by Regulating Skeletal Muscle-Derived Oncogenes and Tumor Suppressors
title_sort high intensity aerobic exercise suppresses cancer growth by regulating skeletal muscle derived oncogenes and tumor suppressors
topic exercise
cancer
RNA-seq
skeletal muscle
tumor suppressors
url https://www.frontiersin.org/articles/10.3389/fmolb.2022.818470/full
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