{'fraction_non_alphanumeric': 0.031208499335989376, 'fraction_numerical': 0.01195219123505976, 'mean_word_length': 5.101214574898785, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
The role of NF‐kappaB in cancer cachexia‐induced skeletal muscle wasting

Recent work points to the involvement of nuclear factor of kappaB (NF‐κB) in cancer cachexia‐induced muscle atrophy, but its exact role in inducing wasting is poorly defined. Elucidation of the specific κB transcription factors and their target genes could generate new treatment strategies for cachexia. We inoculated mice with colon‐26 (C‐26) carcinoma and overexpressed either a κB‐dependent luciferase reporter or a dominant negative κB signaling protein, d.n. inhibitor of kappaB kinase beta (d.n. IKKβ), in the tibialis muscle using direct plasmid injection. We found a 2.5‐fold increase in the activation of the κB reporter in tumor‐bearing vs. non‐tumor‐bearing mice. We also found a 50% attenuation of atrophy at 23 days after tumor inoculation in fibers transfected with d.n. IKKβ vs. non‐transfected fibers. We performed chromatin immunoprecipitation to identify the binding of specific κB transcription factors to genes known to be upregulated during other forms of atrophy to determine if they were upregulated in cachectic muscle. In cachexia, we found increased binding of p65 to κB consensus sites near the transcription start site of Fbxo1 (atrogin), MuRF1, and caspase 3, as well as increased binding of p50 to the same κB sites for MuRF1 and ubiquitin C. The results show the requirement of classical NF‐kB signaling for cancer cachexia and they reveal several NF‐kB transcription factor target genes in cachexia.