Neuregulin1 acts as a suppressor in human lung adenocarcinoma via AKT and ERK1/2 pathway
Youya Wang1,2, Zhifeng Ning3, Xuefeng Zhou1
1Department of Cardiothoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
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.
Insights
Neuregulin1 (NRG1) acts as a tumor suppressor in lung adenocarcinoma (LUAD). Lower NRG1 expression promotes cancer growth, while its restoration inhibits proliferation, migration, and invasion via AKT and ERK pathways.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Neuregulin1 (NRG1) is a critical signaling protein implicated in malignancies.
- NRG1 gene fusions are observed in lung cancer, but its role remains unclear.
- This study focuses on the biological functions of NRG1 in human lung adenocarcinoma (LUAD).
Purpose of the Study:
- To investigate the role of NRG1 in the development of LUAD.
- To elucidate the signaling pathways regulated by NRG1 in LUAD cells.
Main Methods:
- NRG1 expression analyzed in LUAD tissues using Western blot, qRT-PCR, and IHC.
- LUAD cell behavior (proliferation, cell cycle, apoptosis, migration, invasion) assessed after modulating NRG1 levels via exogenous NRG1 or siRNA.
- Underlying signaling pathways (AKT, ERK) investigated by Western blot.
Main Results:
- Lower NRG1 expression was detected in LUAD tissues compared to controls.
- Exogenous NRG1 suppressed LUAD cell proliferation, migration, and invasion.
- Downregulation of endogenous NRG1 promoted these malignant behaviors.
- NRG1 modulation did not significantly affect cell cycle or apoptosis.
- NRG1 deficiency reduced p-ERK1/2 and p-AKT protein levels.
Conclusions:
- NRG1 functions as a suppressor in LUAD development.
- NRG1's tumor-suppressive role is mediated through the AKT and ERK signaling pathways.
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