PMID- 36919755
OWN - NLM
STAT- MEDLINE
DCOM- 20230426
LR  - 20230505
IS  - 1759-7714 (Electronic)
IS  - 1759-7706 (Print)
IS  - 1759-7706 (Linking)
VI  - 14
IP  - 12
DP  - 2023 Apr
TI  - UHMK1 promotes lung adenocarcinoma oncogenesis by regulating the PI3K/AKT/mTOR 
      signaling pathway.
PG  - 1077-1088
LID - 10.1111/1759-7714.14850 [doi]
AB  - 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.
CI  - (c) 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and 
      John Wiley & Sons Australia, Ltd.
FAU - Li, Yongmeng
AU  - Li Y
AD  - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, China.
FAU - Wang, Shuai
AU  - Wang S
AD  - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, China.
FAU - Jin, Kai
AU  - Jin K
AD  - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, China.
FAU - Jin, Wenxing
AU  - Jin W
AD  - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, China.
FAU - Si, Libo
AU  - Si L
AD  - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, China.
FAU - Zhang, Huiying
AU  - Zhang H
AD  - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, China.
FAU - Tian, Hui
AU  - Tian H
AUID- ORCID: 0000-0003-4516-2313
AD  - Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230315
PL  - Singapore
TA  - Thorac Cancer
JT  - Thoracic cancer
JID - 101531441
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (UHMK1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Cell Line, Tumor
MH  - *Adenocarcinoma of Lung/pathology
MH  - Signal Transduction
MH  - *Lung Neoplasms/pathology
MH  - Cell Transformation, Neoplastic
MH  - Carcinogenesis
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Cell Proliferation
MH  - Gene Expression Regulation, Neoplastic
MH  - Protein Serine-Threonine Kinases/metabolism
PMC - PMC10125785
OTO - NOTNLM
OT  - PI3K/AKT/mTOR signaling pathway
OT  - U2AF homology motif kinase 1 (UHMK1)
OT  - lung adenocarcinoma (LUAD)
OT  - metastasis
OT  - proliferation
COIS- The authors declare no competing interests.
EDAT- 2023/03/16 06:00
MHDA- 2023/04/26 06:41
PMCR- 2023/03/15
CRDT- 2023/03/15 06:13
PHST- 2023/02/26 00:00 [revised]
PHST- 2023/02/07 00:00 [received]
PHST- 2023/02/27 00:00 [accepted]
PHST- 2023/04/26 06:41 [medline]
PHST- 2023/03/16 06:00 [pubmed]
PHST- 2023/03/15 06:13 [entrez]
PHST- 2023/03/15 00:00 [pmc-release]
AID - TCA14850 [pii]
AID - 10.1111/1759-7714.14850 [doi]
PST - ppublish
SO  - Thorac Cancer. 2023 Apr;14(12):1077-1088. doi: 10.1111/1759-7714.14850. Epub 2023 
      Mar 15.