Abstract
Backgrounds
Cardiac regeneration may be the future ultimate therapy for terminal
heart failure. Nucleostemin (GNL3) plays a pivotal role in cardiac
repair. Induced pluripotent stem (iPS) cells, induced by SOX2-OCT4-NANOG
complex, may offer clues form regeneration. We would like to explore the
interactions by bioinformatic approach.
We identified the candidates that interacted with nucleostemin (GNL3),
SOX2, OCT4 (POU5F1), and NANOG with NCBI online Entrez Gene and PubMed.
The pathway networks were built with Ingenuity Pathway Analysis (IPA)
7.5 ®.
New Information
In GNL3 network, molecules related to cardiovascular system development
and function included CDKN2A, TP53 (tumor protein p53), ID3, NPM1, and
IL2 (p=8.4e-4 ~ 9.9e-4 by right-tailed Fisher Exact
Test). In canonical pathways, PPP2R5A involved in cardiac
beta-adrenergic signaling and Fgf (fibroblast growth factor) involved in
human embryonic stem cell pluripotency. Nucleostemin and iPS networks
had two common molecules: Fgf and TP53.
Nucleostemin and iPS have interactions via TP53 (tumor protein P53) and
Fgf (fibroblast growth factor), which would require future research.
Objective
Although there are clinical advances in mechanical circulatory support
devices and heart transplantation, the ultimate therapy for a failing
heart may be cardiac regeneration from reprogrammed somatic cells or
induced pluripotent stem cells, which avoids the pitfalls in ethics of
embryonic cells, device anticoagulants, or immunosuppressants. Prior
studies found nucleostemin (GNL3) may play a pivotal role in cardiac
repair. On the other hand, SOX2-OCT4-NANOG complex, the ectopically
induced transcription factors for induced pluripotent stem (iPS) cells,
is the key to stem cell pluripotency. We would like to explore the
interactions by bioinformatic approach as for future molecular
biologists.
Methods
Literature review was done with NCBI online Entrez Gene and PubMed to
identify the candidate molecules that may interact with nucleostemin
(GNL3), SOX2, OCT4 (POU5F1), and NANOG. Ingenuity Pathway Analysis (IPA)
7.5 ® was then used to build the pathway networks exploiting the
interplays of interactions with GNL3 and SOX2-OCT4-NANOG. Functional
analyses of pathophysiological processes as well as canonical pathways
were conducted and integrated.
Results
Functional pathway networks were built for nucleostemin (GNL3), with the
interactions with the iPS (SOX2-OCT4-NANOG) network in the subcellular
level (Figure 1). In the GNL3 network, molecules related to
cardiovascular system development and function were identified: CDKN2A,
TP53 (tumor protein p53), ID3, NPM1, and IL2 (p=8.4e-4 ~
9.9e-4 by right-tailed Fisher Exact Test). In canonical pathways,
PPP2R5A involved in cardiac beta-adrenergic signaling and Fgf
(fibroblast growth factor) involved in human embryonic stem cell
pluripotency. Of note, nucleostemin was found having interactions in
common with NANOG of the iPS networks via two molecules: Fgf and TP53.
Conclusion
In the exploratory analysis, the functional pathway networks of
nucleostemin and iPS interact via TP53 (tumor protein P53) and Fgf
(fibroblast growth factor), which could be further investigated to
provide clues for the future research of postnatal cardiac regeneration.
Figure 1
Nucleostemin (GNL3) and iPS (SOX2-OCT4-NANOG) subcellular interaction
network