Anoctamin 6 Regulates C2C12 Myoblast Proliferation

<div><p>Anoctamin 6 (<i>Ano6</i>) belongs to a conserved gene family (TMEM16) predicted to code for eight transmembrane proteins with putative Ca²⁺-activated chloride channel (CaCC) activity. Recent work revealed that disruption of <i>ANO6</i> leads to a blood coagulation defect and impaired skeletal development. However, its function in skeletal muscle cells remains to be determined. By using a RNA interference mediated (RNAi) loss-of-function approach, we show that <i>Ano6</i> regulates C2C12 myoblast proliferation. <i>Ano6</i> is highly expressed in C2C12 myoblasts and its expression decreases upon differentiation. Knocking down <i>Ano6</i> significantly reduces C2C12 myoblast proliferation but has minimal effect on differentiation. <i>Ano6</i> deficiency significantly reduces ERK/AKT phosphorylation, which has been shown to be involved in regulation of cancer cell proliferation by another Anoctamin member. Taken together, our data demonstrate for the first time that <i>Ano6</i> plays an essential role in C2C12 myoblast proliferation, likely via regulating the ERK/AKT signaling pathway.</p>