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bioRxiv · 10.1101/2021.11.17.469038

Myogenetic oligodeoxynucleotide restores differentiation and reverses inflammation of myoblasts aggravated by cancer-conditioned medium

Nihashi, Y.·Yamamoto, M.·Shimosato, T.·Takaya, T.
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Abstract

Cancer cachexia is characterized by irreversible muscle loss which is a critical factor in the prognosis of cancer patients. Myoblasts are myogenic precursor cells that are required to maintain skeletal muscle tissue. Previous studies have reported that cancer-released factors deteriorate myoblast differentiation, which is one of the causes of cachexia-associated muscle wasting. We recently identified the myogenetic oligodeoxynucleotide iSN04, which acts an anti-nucleolin aptamer and promotes myogenesis. The present study investigated the effects of iSN04 on human myoblasts exposed to conditioned medium (CM) of colon cancer cells. Cancer-CM impaired myogenic differentiation and myotube formation of myoblasts by upregulating the expression of inflammatory cytokines. iSN04 completely reversed cancer-CM-induced deteriorated myogenesis and inflammatory responses in myoblasts. Tumor necrosis factor- (TNF-), a representative cytokine present in cancer-CM, inhibited differentiation and induced inflammation of myoblasts, similar to cancer-CM. Pre-treatment with iSN04 reversed TNF--induced cachectic phenotypic features in myoblasts. These results indicate that iSN04 protects myoblasts against the effects of cancer-released factors and maintain their myogenic activity. This study provides a novel therapeutic strategy to prevent muscle loss associated with cancer cachexia.

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Nihashi, Y., Yamamoto, M., Shimosato, T., Takaya, T.. 2021-11-18. Myogenetic oligodeoxynucleotide restores differentiation and reverses inflammation of myoblasts aggravated by cancer-conditioned medium. https://doi.org/10.1101/2021.11.17.469038

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