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Gene & Protein in Disease Bioinformatics to identify gene signatures of CF

CDC42 belongs to the Rho family of small GTPases and analysis of the genes reported in this study, the RNASEL
has numerous cellular functions. One of the extensively and HDAC4 genes were upregulated, and the WWP2,
characterized roles of CDC42 over the recent decades is CUL1, CDC42, and UBA2 genes were downregulated. This
actin cytoskeleton remodeling. Among the plethora of indicates that CF patients boast elevated expression levels
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cellular functions, CDC42 has been found to involve in of the RNASEL and HDAC4 genes and reduced expression
the endocytosis and reutilizing of some plasma membrane levels of WWP2, CUL1, CDC42, and UBA2 genes. However,
proteins. 47,48 The transducer of the Cdc42-dependent actin it should be noted that the HDAC4, CUL1, RNASEL, and
assembly (Toca) family and the Wiskott–Aldrich syndrome WWP2 genes have never been studied for their individual
protein (WASP) are two examples of downstream effectors involvement in CF development. Thus, independent
that are bound and activated by GTP-bound CDC42. validations should be performed to corroborate their
Through the Arp2/3 complex, they cause actin filaments utility in diagnosis and prognosis evaluation.
to branch. It has been reported that the pharmacological
inhibitor wiskostatin causes a decrease in CFTR protein 6. Conclusion
in cell surface and an inhibition of the CFTR-guided DEGs such as CDC42, UBA2, HDAC4, CUL1, RNASEL, and
chloride currents. On the other hand, studies revealed WWP2, as well as the pathways these genes are enriched
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that CDC42 regulates the initial steps of CFTR biogenesis in such as glutamatergic synapse, basal transcription
and processing, which is crucial for the stability of CFTR factors, nucleotide elimination repair, ubiquitin-mediated
in the plasma membrane. Furthermore, CDC42 signaling proteolysis, cell cycle, and Staphylococcus aureus infection,
47
regulates efferocytosis and Fcγ receptor-mediated might be involved in the pathogenesis of CF. Our findings
phagocytosis in CF. By adding the tiny protein SUMO, the also shed light on the significant roles of CDC42, UBA2,
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ubiquitin-activating enzyme UBA2 modifies proteins post- HDAC4, CUL1, RNASEL, and WWP2 in the pathogenesis
translationally and controls their intracellular localization of CF. Among these genes, WWP2 is a new potential
and structure. UBA2 is considered a candidate modifier of genetic marker for CF that has never been disclosed in
CF phenotype and found to be upregulated in individuals the past. The current set of results offers a theoretical
with severe CF. 51
direction for conducting the subsequent, more in-depth
Researchers have explored the association of histone experiments to substantiate the newly identified markers
deacetylase (HDAC) isoforms with CF, and inhibitors as distinct targets for diagnosis, prognosis, and treatment.
have also been developed against HDACs. 52,53 HDAC4 Moreover, larger sample sizes are needed to validate these
is an HDAC isoform involved in the control of gene findings and pinpoint possible targets for CF treatments.
transcription, cell growth, survival, and proliferation.
54
A variety of cellular dysfunctions are caused by the Acknowledgments
aberrant expression of this enzyme. CUL1 belongs to None.
53
the CULLIN family and provides a scaffold for ubiquitin
ligases that acts an important player in protein degradation Funding
and ubiquitination and regulates the equilibrium between
normal cellular growth and uncontrolled proliferation. None.
55
Studies have identified CUL1 as a validated target gene of Conflict of interest
respiratory diseases such as asthma and chronic obstructive
pulmonary disease. 56-58 The authors declare that they have no competing interests.
RNASEL is a regulated endoribonuclease and mediates Author contributions
antiproliferative, antiviral, and apoptotic effects of the
interferons. Nonetheless, an immunogenicity test Conceptualization: Arafat Rahman Oany
59
using clinical samples from the CF patients revealed that Investigation: Mamun Mia, Arafat Rahman Oany
the RNASEL was expressed comparatively higher in the Writing – original draft: Mamun Mia, Arafat Rahman
unmodified mRNA-treated samples compared to the Oany, Tahmina Pervin
chemical-induced samples. WWP2 is an E3 ubiquitin Writing – review & editing: All authors
60
ligase belonging to the NEDD4-like protein family that Ethics approval and consent to participate
regulates the activation of T cells, transcription, cellular
transport, and the fate of embryonic stem cells. 61,62 Not applicable.
Numerous investigations have revealed WWP2 as an Consent for publication
essential regulatory component in the formation of renal,
pulmonary, and cardiac fibrosis. 63,64 Based on the overall Not applicable.

Volume 3 Issue 2 (2024) 8 doi: 10.36922/gpd.2937