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.

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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