Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy, however less is known specifically on miRNAs in cancer cachexia. PURPOSE: The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. METHODS: Phosphate buffered saline (PBS) or Lewis-Lung carcinoma cells (LLC) were injected into C57BL/6J mice at 8 weeks of age. LLC animals were allowed to develop tumors for 4 weeks to induce cachexia. Tibialis anterior muscles were extracted and processed to isolate small RNAs which were used for miRNA sequencing. Sequencing results were assembled with mature miRNAs and functions of miRNAs were analyzed using Ingenuity Pathway Analysis. RESULTS: LLC animals developed tumors that contributed to significantly smaller tibialis anterior muscles (18.5%) and muscle cross-sectional area (40%) compared to PBS. 371 miRNAs were present in the muscle above background levels. Of these, nine miRNAs were found to be differentially expressed. Significantly altered groups of miRNAs were categorized into primary functionalities including cancer, cell-to-cell signaling, and cellular development among others. Gene network analysis predicted specific alterations of factors contributing to muscle size including Akt, FOXO3 and others. CONCLUSION: These results create a foundation for future research into the sufficiency of targeting these genes to attenuate muscle loss in cancer cachexia.
- muscle wasting
- Copyright © 2017, Physiological Genomics