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Transcriptomics data on muscle atrophy in the state of cancer cachexia, as well as the therapeutic effects of Astragalus membranaceus Decoction

ABSTRACT: Cancer cachexia (CC) causes severe muscle loss in advanced cancer patients, significantly impacting their quality of life and life expectancy. The autophagy-lysosome system is a key pathway in muscle depletion in CC, yet targeted therapies are limited. This study examines how Astragalus polysaccharides (APS) from Astragalus membranaceus alleviate muscle wasting in CC mice. Mice were divided into control, model, and APS high-dose groups. Transcriptomic analysis identified differentially expressed genes (DEGs) enriched in autophagy and mitochondrial autophagy pathways. Results indicate that APS treatment normalizes the expression levels of some DEGs in cachectic muscle tissue. For instance, autophagy-related genes Gabarapl1, Ggad45b, and Igf1r return to normal levels after APS treatment. KEGG pathway analysis suggests that APS modulates the transcription of autophagy- and mitochondrial autophagy-related genes, reducing over-activated autophagy and mitochondrial autophagy activities. Collectively, our data provide additional insights into the transcriptional profiles of cachectic muscle and muscle treated with APS, highlighting the potential of APS as a therapeutic agent for mitigating muscle depletion in cancer cachexia.

ORGANISM(S): Mus musculus

PROVIDER: GSE301467 | GEO | 2025/07/23

REPOSITORIES: GEO

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Project description:Background. Pancreatic Ductal AdenoCarcinoma (PDAC), the most frequent pancreatic cancer, is a deadly cancer since often diagnosed late and resistant to current therapies. A high proportion of PDAC patients are affected by cachexia induced by the tumor. This cachexia, characterized by loss of muscle mass and strength, contributes to patient frailty and poor therapeutic response. We showed that mitochondrial metabolism is reprogrammed in PDAC tumor cell and constitutes a vulnerability, opening novel therapeutic avenues. The objective of the present work was to investigate the molecular mechanisms underlying mitochondrial remodeling in PDAC cachectic skeletal muscle. Methods. Our study focused on the gastrocnemius muscle of genetically-engineered mice developing spontaneously a PDAC associated with cachexia (KIC GEMM). We compared KIC mice developing a pancreatic tumor in 9-10 weeks to control littermates. We did an integrative study combining in vivo functional analyses by non-invasive Magnetic Resonance, and ex-vivo histology, Seahorse, RNA-sequencing, and proteomic mass spectrometry and western blotting analyses. Results. The cachectic KIC PDAC mice show a severe sarcopenia with loss of muscle mass and strength associated with a diminution in muscle fiber’s size and induction of protein degradation processes. Mitochondria in PDAC atrophic muscles show decreased respiratory capacities and structural alterations (“hyperfused” mitochondria), associated with deregulation of oxidative phosphorylation and mitochondrial dynamics pathways at the molecular level. Increased expression of multiple reactive oxygen species (ROS) defense genes suggests oxidative stress prone to affect mitochondrial macromolecules and homeostasis. Interestingly, multiple genes and proteins involved in DNA metabolism pathways, such as DNA damage, degradation of DNA, nucleotide synthesis, and folate pathway were found altered in sarcopenic mitochondria. While the number of mitochondria was not changed, the mitochondrial mass was decreased by a factor of 2 and the mitochondrial DNA by a factor of 3, suggesting a defect in mitochondrial genome homeostasis. Conclusions. We unveiled that mitochondrial alterations in skeletal muscle play a central role in PDAC-induced cachexia. Muscle atrophy is associated with strong mitochondrial metabolic defects that are not limited to carbohydrates and protein, but concern also lipids, ROS and nucleic acids. Our data provide a frame to guide towards the most relevant molecular markers that would be affected at the start of tumor development and could be targets in the clinic to limit PDAC-induced cachexia at early stages of the pathology.

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Transcriptomics data on muscle atrophy in the state of cancer cachexia, as well as the therapeutic effects of Astragalus membranaceus Decoction

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