Downregulation of AHNAK2 inhibits cell cycle of lung adenocarcinoma cells by interacting with RUVBL1
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Updated: Jul 26, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Xin Li1, Hui Li2, Ming-Ming Shao3
1Beijing Chaoyang Hospital, Beijing, China.
Background:
Lung adenocarcinoma (LUAD) is the leading cause of death among cancer diseases. The tumorigenic functions of AHNAK2 in LUAD have attracted more attention in recent years, while there are few studies which have reported its high molecular weight.
Methods:
The mRNA-seq data of AHNAK2 and corresponding clinical data from UCSC Xena and GEO was analyzed. LUAD cell lines were transfected with sh-NC and sh-AHNAK2, and cell proliferation, migration and invasion were then detected by in vitro experiments. We performed RNA sequencing and mass spectrometry analysis to explore the downstream mechanism and interacting proteins of AHNAK2. Finally, western blot, cell cycle analysis and CO-IP were used to confirm our assumptions regarding previous experiments.
Results:
Our study revealed that AHNAK2 expression was significantly higher in tumors than in normal lung tissues and higher AHNAK2 expression led to a poor prognosis, especially in patients with advanced tumors. AHNAK2 suppression via shRNA reduced the LUAD cell lines proliferation, migration and invasion and induced significant changes in DNA replication, NF-kappa B signaling pathway and cell cycle. AHNAK2 knockdown also caused G1/S phase cell cycle arrest, which could be attributed to the interaction of AHNAK2 and RUVBL1. In addition, the results from gene set enrichment analysis (GSEA) and RNA sequencing suggested that AHNAK2 probably plays a part in the mitotic cell cycle.
Conclusion:
AHNAK2 promotes proliferation, migration and invasion in LUAD and regulates the cell cycle via the interaction with RUVBL1. More studies of AHNAK2 are still needed to reveal its upstream mechanism.
Insights
The protein AHNAK2 promotes lung adenocarcinoma (LUAD) growth and spread. Inhibiting AHNAK2 halts LUAD cell proliferation and migration, offering potential therapeutic targets for this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Lung adenocarcinoma (LUAD) is a leading cause of cancer mortality.
- The role of AHNAK2 in LUAD tumorigenesis is increasingly recognized, yet its high molecular weight functions remain understudied.
Purpose of the Study:
- To investigate the role and molecular mechanisms of AHNAK2 in lung adenocarcinoma.
- To explore the impact of AHNAK2 on LUAD cell behavior and prognosis.
Main Methods:
- Analysis of mRNA-seq and clinical data from public databases (UCSC Xena, GEO).
- In vitro studies involving LUAD cell lines with AHNAK2 suppression (shRNA).
- RNA sequencing, mass spectrometry, western blot, cell cycle analysis, and co-immunoprecipitation (CO-IP) to elucidate mechanisms.
Main Results:
- AHNAK2 expression is elevated in LUAD tissues and correlates with poor prognosis, particularly in advanced stages.
- AHNAK2 suppression reduced LUAD cell proliferation, migration, and invasion, impacting DNA replication, NF-kappa B signaling, and cell cycle.
- Knockdown of AHNAK2 induced G1/S phase cell cycle arrest, linked to its interaction with RUVBL1, and suggested involvement in the mitotic cell cycle.
Conclusions:
- AHNAK2 significantly promotes proliferation, migration, and invasion in LUAD.
- AHNAK2 regulates the cell cycle in LUAD through interaction with RUVBL1.
- Further research is needed to fully understand the upstream regulatory mechanisms of AHNAK2 in LUAD.
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