MiR-770 inhibits tumorigenesis and EMT by targeting JMJD6 and regulating WNT/β-catenin pathway in non-small cell lung cancer

Abstract

AimsMicroRNAs (miRNAs) plays important role in development and disease, especially in cancer including non-small cell lung cancer (NSCLC). However, the role of miR-770 in NSCLC remains unclear. In this study, we aimed to study the function and mechanism of miR-770 in tumorigenesis of NSCLC. Main methodsRT-qPCR was used to measure the expression levels of miR-770 in NSCLC tissues and cells. MTT assay, colony formation assay, flow cytometric analysis and transwell migration and invasion assays were performed to investigate the role of miR-770 in NSCLC cells. Bioinformatics and luciferase reporter analyses were used to demonstrate that whether the Jumonji domain-containing 6 (JMJD6) as a direct target of miR-770. The function of JMJD6 in NSCLC was also investigated. Finally, in vivo animal experiment was used to study whether miR-770 was capable of inhibiting tumor growth by inhibiting JMJD6. Key findingsWe first showed that miR-770 was downregulated in NSCLC tissues and cell lines, and the low expression of miR-770 was correlated with poor patient survival in NSCLC patients. miR-770 acted on a tumor suppressor by binding to the 3′UTR of JMJD6 and downregulated its expression in NSCLC cells. This study also demonstrated that JMJD6 played as an oncogene in NSCLC cells. miR-770 overexpression was capable of inhibiting NSCLC tumor growth by inhibiting JMJD6 and its downstream WNT/β-catenin pathway both in vitro and in vivo. SignificanceThe present study indicated that miR-770 functioned as a tumor suppressor and it might be a potential biomarker and therapeutic target in NSCLC.