title: MiRNA-638 promotes autophagy and malignant phenotypes of cancer cells via directly suppressing DACT3.
abstract: 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.
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China; College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liang
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Pan
authors.affiliation: Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: aaryoung@yeah.net.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C514671:Dact3 protein, mouse; D035683:MicroRNAs
keywords: Autophagy; Breast cancer; DACT3; Esophageal cancer; miR-638