Original ArticleMiRNA-638 promotes autophagy and malignant phenotypes of cancer cells via directly suppressing DACT3

- miR-638 overexpression promotes starvation- and rapamycin-induced autophagy.
- As an oncogene, miR-638 promotes malignant properties of esophageal and breast cancer cells.
- The miR-638-DACT3 axis might be important in controlling and autophagy and tumorigenesis.

Dyregulation of autophagy is implicated in human cancers and the mechanism details remains largely unclear. Herein we report the regulatory role of miR-638 in autophagy of esophageal squamous cell carcinoma (ESCC) and breast cancer cells. We found that miR-638 overexpression promotes starvation- and rapamycin-induced autophagy. In ESCC and breast cancer cells, miR-638 acts as an oncogene and promotes cell proliferation, migration, as well as invasion in vitro and in vivo. In accordance with this, we observed significantly higher miR-638 expression in ESCC and breast cancer tissues compared to normal tissues. To further elucidate regulatory mechanisms of miR-638 in autophagy, we performed a computational nomination of its target genes through intersecting the results of multiple prediction algorithms. DACT3, a key regulator of Wnt/β-catenin signaling, was predicted to be regulated by miR-638 by all programs and confirmed by experimental results. Depletion of DACT3 phenocopied effects of miR-638 overexpression, demonstrating its importance in autophagy. These results elucidate that the miR-638-DACT3 axis might be an important molecular pathway in controlling autophagy and tumorigenesis. Our data in clinical tissue samples highlight miR-638 and DACT3 as histological marker for cancer detection and their potentially therapeutic implications.