Mist1 mediates basal autophagy flux through direct regulation of FIP200 in malignant melanoma cell lines

Malignant melanoma (MM) is a highly aggres‐ sive dermatological malignancy with a high tendency to metastasize and a character of refractoriness to conventional treatments after metastasis, which is associated with poor prognosis. For developing more effective therapies, and also for identification of novel biomarkers to predict the behaviour of MM, it is required to fully understand the precise mecha‐ nisms underlying melanoma development and progression. The present study compared the expression of muscle, intestine and stomach expression 1 (Mist1) in melanoma cell lines and normal human epidermal melanocytes (NHEM693). It was identified that Mist1 was overexpressed in melanoma cell lines compared with that in NHEM (P<0.05). Mist1 was induced by nutrient starvation in the present study. In eukaryotic cells, autophagy was activated to promote the survival of cells during nutrient starvation. At the same time, the overexpres‐ sion of Mist1 promoted autophagy flux in human malignant melanoma cells. In addition, loss of Mist1 impaired cellular survival under nutrient starvation conditions. These findings highlighted the importance of Mist1 in cellular autophagy in human malignant melanoma cells. It was also elucidated that FAK family kinase‐interacting protein of 200 kDa (FIP200) is a down‐stream signaling protein of Mist1. Mist1 regulated cellular autophagy by directly controlling the expression of autophagy gene FIP200. Furthermore, the CCAGCTGC sequence was then uncovered as the binding site of Mist1 in the core region of the FIP200 promoter. The present study suggests that Mist1 has a functional role in promoting mela‐ noma cell autophagy, and that therapeutic strategies directed towards interfering with the action of this gene may be effec‐ tive for reducing the incidence or development of human melanoma.