PMID- 29991672
OWN - NLM
STAT- MEDLINE
DCOM- 20181217
LR  - 20240204
IS  - 0219-1032 (Electronic)
IS  - 1016-8478 (Print)
IS  - 1016-8478 (Linking)
VI  - 41
IP  - 8
DP  - 2018 Aug 31
TI  - Integrative Profiling of Alternative Splicing Induced by U2AF1 S34F Mutation in 
      Lung Adenocarcinoma Reveals a Mechanistic Link to Mitotic Stress.
PG  - 733-741
LID - 10.14348/molcells.2018.0176 [doi]
AB  - Mutations in spliceosome components have been implicated in carcinogenesis of 
      various types of cancer. One of the most frequently found is U2AF1 S34F missense 
      mutation. Functional analyses of this mutation have been largely limited to 
      hematological malignancies although the mutation is also frequently seen in other 
      cancer types including lung adenocarcinoma (LUAD). We examined the impact of 
      knockdown (KD) of wild type (wt) U2AF1 and ectopic expression of two splice 
      variant S34F mutant proteins in terms of alternative splicing (AS) pattern and 
      cell cycle progression in A549 lung cancer cells. We demonstrate that induction 
      of distinct AS events and disruption of mitosis at distinct sub-stages result 
      from KD and ectopic expression of the mutant proteins. Importantly, when compared 
      with the splicing pattern seen in LUAD patients with U2AF1 S34F mutation, ectopic 
      expression of S34F mutants but not KD was shown to result in common AS events in 
      several genes involved in cell cycle progression. Our study thus points to an 
      active role of U2AF1 S34F mutant protein in inducing cell cycle dysregulation and 
      mitotic stress. In addition, alternatively spliced genes which we describe here 
      may represent novel potential markers of lung cancer development.
FAU - Kim, Suyeon
AU  - Kim S
AD  - Ewha Research Center for Systems Biology (ERCSB), Seoul 03760, Korea.
AD  - Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
FAU - Park, Charny
AU  - Park C
AD  - Research Institute, National Cancer Center, Goyang 10408, Korea.
FAU - Jun, Yukyung
AU  - Jun Y
AD  - Ewha Research Center for Systems Biology (ERCSB), Seoul 03760, Korea.
AD  - Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
FAU - Lee, Sanghyuk
AU  - Lee S
AD  - Ewha Research Center for Systems Biology (ERCSB), Seoul 03760, Korea.
AD  - Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
FAU - Jung, Yeonjoo
AU  - Jung Y
AD  - Ewha Research Center for Systems Biology (ERCSB), Seoul 03760, Korea.
AD  - Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
FAU - Kim, Jaesang
AU  - Kim J
AD  - Ewha Research Center for Systems Biology (ERCSB), Seoul 03760, Korea.
AD  - Department of Life Science, Ewha Womans University, Seoul 03760, Korea.
LA  - eng
GR  - Ministry of Science and ICT/
GR  - 2013M3C7A1056562/National Research Foundation/
GR  - 2015K1A4A3047851/National Research Foundation/
GR  - 2016R1A6A3A11932702/National Research Foundation/
PT  - Journal Article
DEP - 20180710
PL  - United States
TA  - Mol Cells
JT  - Molecules and cells
JID - 9610936
RN  - 0 (Splicing Factor U2AF)
RN  - 0 (U2AF1 protein, human)
SB  - IM
MH  - A549 Cells
MH  - Adenocarcinoma of Lung/*genetics/metabolism/pathology
MH  - Alternative Splicing
MH  - Base Sequence
MH  - Cell Cycle/genetics
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Male
MH  - Mitosis/genetics
MH  - *Mutation
MH  - Splicing Factor U2AF/biosynthesis/*genetics
MH  - Transfection
PMC - PMC6125417
OTO - NOTNLM
OT  - S34F
OT  - U2AF1
OT  - alternative splicing
OT  - lung adenocarcinoma
OT  - mitotic stress
EDAT- 2018/07/12 06:00
MHDA- 2018/12/18 06:00
PMCR- 2018/08/31
CRDT- 2018/07/12 06:00
PHST- 2018/04/22 00:00 [received]
PHST- 2018/05/30 00:00 [revised]
PHST- 2018/05/30 00:00 [accepted]
PHST- 2018/07/12 06:00 [pubmed]
PHST- 2018/12/18 06:00 [medline]
PHST- 2018/07/12 06:00 [entrez]
PHST- 2018/08/31 00:00 [pmc-release]
AID - S1016-8478(23)00544-7 [pii]
AID - molce-41-8-733 [pii]
AID - 10.14348/molcells.2018.0176 [doi]
PST - ppublish
SO  - Mol Cells. 2018 Aug 31;41(8):733-741. doi: 10.14348/molcells.2018.0176. Epub 2018 
      Jul 10.