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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.8
- 수록면
- 733 - 741 (9page)
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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 hemato-logical 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.
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참고문헌 (20)
참고문헌 신청
Brooks, A.N. / 2014 / A pan-cancer analysis of transcriptome changes associated with somatic mutations in U2AF1 reveals commonly altered splicing events / PLoS One 9:e87361
Damm, F. / 2012 / Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes / Blood 119:3211~3218
Duijf, P.H. / 2013 / The cancer biology of wholechromosome instability / Oncogene 32:4727~4736
Fu, Y. / 2011 / AGdependent 3-splice sites are predisposed to aberrant splicing due to a mutation at the first nucleotide of an exon / Nucleic Acids Res 39:4396~4404
Futreal, P.A. / 2004 / A census of human cancer genes / Nat. Rev. Cancer 4:177~183
Damm, F. / 2012 / Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes / Blood 119:3211~3218
Duijf, P.H. / 2013 / The cancer biology of wholechromosome instability / Oncogene 32:4727~4736
Fu, Y. / 2011 / AGdependent 3-splice sites are predisposed to aberrant splicing due to a mutation at the first nucleotide of an exon / Nucleic Acids Res 39:4396~4404
Futreal, P.A. / 2004 / A census of human cancer genes / Nat. Rev. Cancer 4:177~183
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