UHMK1 promotes lung adenocarcinoma oncogenesis by regulating the PI3K/AKT/mTOR signaling pathway
Yongmeng Li1, Shuai Wang1, Kai Jin1
1Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Background:
Effective targeted therapy for lung adenocarcinoma (LUAD), the number one cancer killer worldwide, continues to be a difficult problem because of the limitation of number of applicable patients and acquired resistance. Identifying more promising drug targets for LUAD treatment holds immense clinical significance. Recent studies have revealed that the U2 auxiliary factor (U2AF) homology motif kinase 1 (UHMK1) is a robust pro-oncogenic factor in many cancers. However, its biological functions and the underlying molecular mechanisms in LUAD have not been investigated.
Methods:
The UHMK1 expression in LUAD cells and tissues was evaluated by bioinformatics analysis, immunohistochemistry (IHC), western blotting (WB), and real time quantitative polymerase chain reaction (RT-qPCR) assays. A series of gain- and loss-of-function experiments for UHMK1 were carried out to investigate its biological functions in LUAD in vitro and in vivo. The mechanisms underlying UHMK1's effects in LUAD were analyzed by transcriptome sequencing and WB assays.
Results:
UHMK1 expression was aberrantly elevated in LUAD tumors and cell lines and positively correlated with tumor size and unfavorable patient prognosis. Functionally, UHMK1 displayed robust pro-oncogenic capacity in LUAD and mechanistically exerted its biological effects via the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway.
Conclusion:
UHMK1 is a potent oncogene in LUAD. Targeting UHMK1 may significantly improve the effect of LUAD treatment via inhibiting multiple biological ways of LUAD progression.
Insights
U2 auxiliary factor (U2AF) homology motif kinase 1 (UHMK1) is elevated in lung adenocarcinoma (LUAD), promoting cancer progression. Targeting UHMK1 may offer a new therapeutic strategy for LUAD patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Lung adenocarcinoma (LUAD) poses a significant global health challenge due to limited effective targeted therapies and acquired resistance.
- Identifying novel drug targets is crucial for improving LUAD treatment outcomes.
- U2 auxiliary factor (U2AF) homology motif kinase 1 (UHMK1) is recognized as a pro-oncogenic factor in various cancers, but its role in LUAD remains unexplored.
Purpose of the Study:
- To investigate the biological functions and molecular mechanisms of UHMK1 in lung adenocarcinoma.
- To determine the clinical significance of UHMK1 expression in LUAD patients.
Main Methods:
- Bioinformatic analysis, immunohistochemistry (IHC), western blotting (WB), and RT-qPCR were used to assess UHMK1 expression in LUAD.
- Gain- and loss-of-function experiments were conducted in vitro and in vivo to evaluate UHMK1's biological roles.
- Transcriptome sequencing and WB assays were employed to elucidate the underlying molecular mechanisms.
Main Results:
- UHMK1 expression was significantly upregulated in LUAD tissues and cell lines.
- Elevated UHMK1 levels correlated with larger tumor size and poorer patient prognosis.
- UHMK1 demonstrated potent oncogenic activity in LUAD, primarily through the PI3K/AKT/mTOR signaling pathway.
Conclusions:
- UHMK1 functions as a potent oncogene in lung adenocarcinoma.
- Targeting UHMK1 presents a promising therapeutic strategy to inhibit LUAD progression through multiple biological pathways.
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