Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C1864663 (
HCC
)
2,985
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:A human-specific switch of alternatively spliced
AFMID
isoforms contributes to
TP53
mutations and tumor recurrence in hepatocellular carcinoma. 2944 9
