MiR-182 promotes cell proliferation by suppressing FBXW7 and FBXW11 in non-small cell lung cancer

MicroRNAs have been found to be deregulated in lung cancers, which play crucial roles in tumorigenesis and progression. FBXW7 and FBXW11, two important F-box proteins of the ubiquitin-proteasome system (UPS), can target multiple substrates for degradation, in order to regulate cell proliferation and survival in cancers. In the present study, we aimed to explore the potential role and regulating mechanism of miR-182 in non-small cell lung cancer (NSCLC).

MiRNA expression was evaluated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). FBXW7, FBXW11, c-Jun, c-Myc and cyclin D protein levels were detected by western blot. Cell growth was determined using cell counting kit (CCK)-8 reagent and colony formation experiment. Then, cell apoptosis and the cell cycle were analyzed on flow cytometry. The target binding activity of miR-182 with FBXW7 or FBXW11 was evaluated through the Dual-Luciferase Reporter Assay System.

It was confirmed that miR-182 was significantly upregulated in tumor tissues, compared with adjacent normal tissues, and this was inversely correlated to the protein levels of FBXW7 and FBXW11. The overexpression of miR-182 in NSCLC cells dramatically promoted cell growth, colony formation capacity and cell cycle progression, and inhibited apoptosis in NSCLC cells. In contrast, the downregulation of miR-182 significantly alleviated these properties in vitro. Furthermore, we demonstrated that miR-182 exerted an oncogenic role in NSCLC by directly targeting FBXW7 and FBXW11.

These results bring new insights into the oncogenic role of miR-182 in NSCLC, indicating that miR-182 might be a novel biomarker for the diagnosis and prognosis of NSCLC.