miR-489-3p promotes malignant progression of non-small cell lung cancer through the inactivation of Wnt/β-catenin signaling pathway via regulating USP48

Background: Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer globally, with average age of cancer patients becoming younger gradually. It is of significance to gain a comprehensive understanding of molecular mechanism underlying NSCLC. Methods: Quantitative polymerase chain reaction (qPCR) and western blot were applied to measure RNA and protein levels separately. Functional assays and western blot were performed to determine the effects of miR-489-3p and USP48 on cell growth, migration and epithelial-mesenchymal transition (EMT) in NSCLC. TOP/FOP flash luciferase reporter assay was carried out to detect the activity of Wnt pathway. Besides, qPCR, RNA pulldown and luciferase reporter assays were conducted to probe into the target gene of miR-489-3p. Immunoprecipitation-western blot (IP-western blot) analysis was implemented to assess the effect of USP48 on the ubiquitination of beta-catenin. Results: miR-489-3p hampers NSCLC cell proliferation, migration and EMT in vitro and NSCLC tumorigenesis and metastasis in vivo. Additionally, miR-489-3p inactivates Wnt/beta-catenin signaling pathway and regulates USP48 to inhibit the ubiquitination of beta-catenin. Moreover, USP48 propels the development of NSCLC cells. Conclusions: The current study demonstrated that miR-489-3p promotes the malignant progression of NSCLC cells via targeting USP48, which might offer a new perspective into NSCLC treatment.

Automated summary

This study found that miR-489-3p promotes the malignant progression of NSCLC by targeting USP48 and inhibiting the Wnt/β-catenin signaling pathway. This discovery provides a new perspective for the treatment of NSCLC.