miR-141-3p inhibits fibroblast proliferation and migration by targeting GAB1 in keloids

• Published in: Biochemical and biophysical research communications 2017-08, Vol.490 (2), p.302-308
• Main Authors: Feng, Jingjuan, Xue, Siliang, Pang, Qiuyu, Rang, Zhen, Cui, Fan
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - genetics; ANIMAL TISSUES; APOPTOSIS; Apoptosis - genetics; BIOLOGICAL RECOVERY; Cell Cycle - genetics; Cell Movement - genetics; Cell Proliferation - genetics; Cells, Cultured; FIBROBLASTS; Fibroblasts - cytology; Fibroblasts - metabolism; GAB1; GROWTH FACTORS; Humans; Keloid - metabolism; Keloids; MicroRNAs - genetics; Migration; miR-141-3p; NEOPLASMS; PATHOGENESIS; Proliferation; RECEPTORS; SKIN
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.06.040

Keloids are benign dermal fibroproliferative tumors that develop as a result of several dysregulated processes. Emerging evidence has revealed that miRNAs contribute to keloid formation. However, the molecular mechanisms of keloid pathogenesis remain unclear. In our study, we found that miR-141-3p in keloid tissues and keloid fibroblasts was significantly decreased compared with the levels in normal tissues and normal skin fibroblasts, respectively. miR-141-3p overexpression resulted in significantly decreased proliferation and migration and the promotion of apoptosis in keloid fibroblasts, whereas miR-141-3p knockdown in keloid fibroblasts yielded the opposite results. Growth factor receptor binding 2-associated binding protein 1 (GAB1) was identified and confirmed as a direct target of miR-141-3p. The expression of GAB1 was up-regulated in keloid tissues, and the restoration of GAB1 partially reversed the inhibitory effects of miR-141-3p on the proliferation and migration of keloid fibroblasts. All data suggested that miR-141-3p decreased the proliferation and migration of keloid fibroblasts by repressing GAB1 expression, providing a useful target for keloid management. •miR-141-3p is down-regulated in human keloids and suppresses keloid fibroblast proliferation.•miR-141-3p induces keloid fibroblast apoptosis and inhibits cell migration.•GAB1 is a direct target of miR-141-3p.•miR-141-3p inhibits keloid fibroblast proliferation and migration by negatively regulating GAB1 expression.