Affiliation:
1. Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan China
Abstract
AbstractBackgroundEffective 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.MethodsThe 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.ResultsUHMK1 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.ConclusionUHMK1 is a potent oncogene in LUAD. Targeting UHMK1 may significantly improve the effect of LUAD treatment via inhibiting multiple biological ways of LUAD progression.
Funder
Natural Science Foundation of Shandong Province
Subject
Pulmonary and Respiratory Medicine,Oncology,General Medicine
Cited by
2 articles.
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