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-α (TNF-α), a representative cytokine present in cancer-CM, inhibited differentiation and induced inflammation of myoblasts, similar to cancer-CM. Pre-treatment with iSN04 reversed TNF-α-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.
Competing Interest Statement
Shinshu University have been assigned the invention of myoDNs by TT, Koji Umezawa, and TS, and filed Japan Patent Application 2018-568609 on February 15, 2018.