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Down-Regulation of AHNAK2 Inhibits Cell Proliferation, Migration and Invasion Through Inactivating the MAPK Pathway
Dong-Wei Wang1, Hai-Zheng Zheng2, Na Cha1
1Department of Pathology, Changchun Obstetrics-Gynecology Hospital, Nanguan District, Changchun, Jilin, China.
Abstract:
AHNAK nucleoprotein 2 (AHNAK2) has been emerged as a crucial protein for neuroblast differentiation and cell migration, thereby involving in the development of various cancers. However, the specific molecular mechanism of AHNAK2 in lung adenocarcinoma is inconclusive. By accessing to the Oncomine dataset and GEPIA website, a higher expression level of AHNAK2 was observed in lung adenocarcinoma tissue samples. Overall survival (OS) curve plotted by Kaplan-Meier method showed that up-regulation of AHNAK2 was related with poor prognosis of lung adenocarcinoma patients. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis and western blot were conducted to examine the expression level of genes in lung adenocarcinoma cells. Through functional in vitro experiments, cell proliferation, migration and invasion were all suppressed after AHNAK2 knockdown using Cell counting kit-8 (CCK-8) assay, wound-healing and transwell analysis. Reduction of AHNAK2 decreased the apoptosis rate using flow cytometry analysis. Moreover, the key markers of MAPK pathway, p-MEK, p-ERK and p-P90RSK were decreased due to the transfection of si-AHNAK2 in A549 cells. U0126, a MEK inhibitor, showed the similar effects on MAPK-related protein levels with si-AHNAK2. To sum up, AHNAK2 is significantly increased in lung adenocarcinoma and plays a carcinogenic role by activating the MAPK signaling pathway, providing a novel insight and raising possibility for lung adenocarcinoma treatment.
Insights
AHNAK2 protein is elevated in lung adenocarcinoma, promoting cancer progression by activating the MAPK pathway. Reducing AHNAK2 inhibits tumor growth, migration, and invasion, offering a potential therapeutic target for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- AHNAK nucleoprotein 2 (AHNAK2) is implicated in neuroblast differentiation and cancer development.
- The precise role of AHNAK2 in lung adenocarcinoma pathogenesis remains unclear.
Purpose of the Study:
- To investigate the molecular mechanism and clinical significance of AHNAK2 in lung adenocarcinoma.
- To explore AHNAK2's role in tumor progression and its association with the MAPK signaling pathway.
Main Methods:
- Bioinformatic analysis using Oncomine and GEPIA datasets.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot.
- In vitro functional assays including CCK-8, wound-healing, transwell, and flow cytometry.
- Gene knockdown using si-AHNAK2 and pathway inhibition with U0126.
Main Results:
- AHNAK2 expression is significantly upregulated in lung adenocarcinoma tissues and correlates with poor patient prognosis.
- AHNAK2 knockdown suppressed cell proliferation, migration, invasion, and induced apoptosis in lung adenocarcinoma cells.
- AHNAK2 activation of the MAPK pathway (p-MEK, p-ERK, p-P90RSK) was confirmed, with similar effects observed upon MEK inhibition.
Conclusions:
- AHNAK2 acts as an oncogene in lung adenocarcinoma by promoting cell proliferation, migration, and invasion via MAPK pathway activation.
- AHNAK2 represents a potential therapeutic target for lung adenocarcinoma treatment.
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