摘要
Pre-mRNA splicing can contribute to the switch of cell identity that occurs in carcinogenesis. Here, we analyze a large collection of RNA-seq data sets and report that splicing changes in hepatocyte-specific enzymes, such as AFMID and KHK, are associated with HCC patients' survival and relapse. The switch of AFMID isoforms is an early event in HCC development and is associated with driver mutations in TP53 and ARID1A. The switch of AFMID isoforms is human-specific and not detectable in other species, including primates. Finally, we show that overexpression of the full-length AFMID isoform leads to a higher NAD+ level, lower DNA-damage response, and slower cell growth in HepG2 cells. The integrative analysis uncovered a mechanistic link between splicing switches, de novo NAD+ biosynthesis, driver mutations, and HCC recurrence.
原文 | 英語 |
---|---|
頁(從 - 到) | 275-284 |
頁數 | 10 |
期刊 | Genome Research |
卷 | 28 |
發行號 | 3 |
DOIs | |
出版狀態 | 已發佈 - 三月 1 2018 |
指紋
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
引用此文
A human-specific switch of alternatively spliced AFMID isoforms contributes to TP53 mutations and tumor recurrence in hepatocellular carcinoma. / Lin, Kuan Ting; Ma, Wai Kit; Scharner, Juergen; Liu, Yun Ru; Krainer, Adrian R.
於: Genome Research, 卷 28, 編號 3, 01.03.2018, p. 275-284.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - A human-specific switch of alternatively spliced AFMID isoforms contributes to TP53 mutations and tumor recurrence in hepatocellular carcinoma
AU - Lin, Kuan Ting
AU - Ma, Wai Kit
AU - Scharner, Juergen
AU - Liu, Yun Ru
AU - Krainer, Adrian R.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Pre-mRNA splicing can contribute to the switch of cell identity that occurs in carcinogenesis. Here, we analyze a large collection of RNA-seq data sets and report that splicing changes in hepatocyte-specific enzymes, such as AFMID and KHK, are associated with HCC patients' survival and relapse. The switch of AFMID isoforms is an early event in HCC development and is associated with driver mutations in TP53 and ARID1A. The switch of AFMID isoforms is human-specific and not detectable in other species, including primates. Finally, we show that overexpression of the full-length AFMID isoform leads to a higher NAD+ level, lower DNA-damage response, and slower cell growth in HepG2 cells. The integrative analysis uncovered a mechanistic link between splicing switches, de novo NAD+ biosynthesis, driver mutations, and HCC recurrence.
AB - Pre-mRNA splicing can contribute to the switch of cell identity that occurs in carcinogenesis. Here, we analyze a large collection of RNA-seq data sets and report that splicing changes in hepatocyte-specific enzymes, such as AFMID and KHK, are associated with HCC patients' survival and relapse. The switch of AFMID isoforms is an early event in HCC development and is associated with driver mutations in TP53 and ARID1A. The switch of AFMID isoforms is human-specific and not detectable in other species, including primates. Finally, we show that overexpression of the full-length AFMID isoform leads to a higher NAD+ level, lower DNA-damage response, and slower cell growth in HepG2 cells. The integrative analysis uncovered a mechanistic link between splicing switches, de novo NAD+ biosynthesis, driver mutations, and HCC recurrence.
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UR - http://www.scopus.com/inward/citedby.url?scp=85046107018&partnerID=8YFLogxK
U2 - 10.1101/gr.227181.117
DO - 10.1101/gr.227181.117
M3 - Article
AN - SCOPUS:85046107018
VL - 28
SP - 275
EP - 284
JO - Genome Research
JF - Genome Research
SN - 1088-9051
IS - 3
ER -