Neuregulin1 acts as a suppressor in human lung adenocarcinoma via AKT and ERK1/2 pathway.

ABSTRACT

BACKGROUND: Neuregulin1 (NRG1) is critical signaling protein that mediates the activation of downstream signaling pathways associated with malignancies. Multiple gene fusions related to NRG1 have been found in lung cancer. However, the underlying role NRG1 in lung cancer is yet unclear. Therefore, the present study investigated the biological functions on human lung adenocarcinoma (LUAD). METHODS: The expression of NRG1 was detected in LUAD tissues by Western blot (WB), quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The expression of NRG1 was upregulated by the addition of exogenous NRG1 and downregulated by small interfering RNA (siRNA), and the biological behaviors of LUAD cells were assessed cell proliferation by MTT assay, cell cycle and apoptosis by flow cytometry analysis, and migration and invasion using Transwell system. Finally, the pathway underlying the cellular function was analyzed by WB. RESULTS: A lower expression of NRG1 was observed in LUAD cancer tissues (P<0.05). Moreover, the addition of exogenous NRG1 reduced the cell proliferation, migration, and invasion (P<0.001), while the downregulation of endogenous NRG1 promoted the three kinds of biological behaviors of LUAD cell lines (P<0.001); however, these manifestations did no effect on the distribution of cell cycle and apoptosis status (P>0.05). Furthermore, the deficiency of NRG1 reduced the expression of p-ERK1/2 and p-AKT at the protein level (P<0.001). CONCLUSIONS: The current results suggested that NRG1 might be a suppressor in the development of LUAD, and its function was related to AKT and ERK1/2 pathway.