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

miR-489-3p通过调控USP48失活Wnt/β-catenin信号通路促进非小细胞肺癌恶性进展

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作者:Pei Zhang #, Li Li #, Bing Wang, Xu Ran, Shengrong Yang, Yujie Luo, Yunhe Li, Zhenghong Wang, Yi Liu, Bing Zhu

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.

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.

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 β-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/β-catenin signaling pathway and regulates USP48 to inhibit the ubiquitination of β-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.

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