Role of a small GTPase Cdc42 in aging and age-related diseases

Umbayev, Bauyrzhan; Safarova, Yuliya; Yermekova, Aislu; Nessipbekova, Assem; Syzdykova, Aizhan; Askarova, Sholpan

doi:10.1007/s10522-022-10008-9

Cited by 14 publications

(9 citation statements)

References 191 publications

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“…MAPK6/MAPK4 signaling regulates cell morphology, migration, endocytosis, and cell cycle progression, and its dysregulation is a known marker of cancer ( 24 ). Interestingly, cell polarity determinant CDC42 controls division symmetry to block leukemia cell differentiation and is involved in AML development ( 25 ), while CDC42 GTPase cycle signaling is a known player in aging and age-related diseases ( 26 ), nominating these genes as valuable markers for further investigation.…”

Section: Resultsmentioning

confidence: 99%

Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia

Ramakrishnan,

Datta,

Panja

et al. 2023

Front. Oncol.

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IntroductionChronological aging is a well-recognized diagnostic and prognostic factor in multiple cancer types, yet the role of biological aging in manifesting cancer progression has not been fully explored yet.MethodsGiven the central role of chronological aging in prostate cancer and AML incidence, here we investigate a tissue-specific role of biological aging in prostate cancer and AML progression. We have employed Cox proportional hazards modeling to associate biological aging genes with cancer progression for patients from specific chronological aging groups and for patients with differences in initial cancer aggressiveness.ResultsOur prostate cancer-specific investigations nominated four biological aging genes (CD44, GADD45B, STAT3, GFAP) significantly associated with time to disease progression in prostate cancer in Taylor et al. patient cohort. Stratified survival analysis on Taylor dataset and validation on an independent TCGA and DKFZ PRAD patient cohorts demonstrated ability of these genes to predict prostate cancer progression, especially for patients with higher Gleason score and for patients younger than 60 years of age. We have further tested the generalizability of our approach and applied it to acute myeloid leukemia (AML). Our analysis nominated three AML-specific biological aging genes (CDC42EP2, CDC42, ALOX15B) significantly associated with time to AML overall survival, especially for patients with favorable cytogenetic risk score and for patients older than 56 years of age.DiscussionComparison of the identified PC and AML markers to genes selected at random and to known markers of progression demonstrated robustness of our results and nominated the identified biological aging genes as valuable markers of prostate cancer and AML progression, opening new avenues for personalized therapeutic management and potential novel treatment investigations.

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Section: Resultsmentioning

confidence: 99%

Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia

Ramakrishnan,

Datta,

Panja

et al. 2023

Front. Oncol.

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“…CDC42 is a small GTPase involved in a great number of biological regulations. Recent studies have indicated that the dysregulation of CDC42 caused aging in somatic and stem cells, and lead to age-related diseases such as neurodegenerative and cardiovascular dysfunctions [ 68 , 69 ]. KRAS is also an oncogene, the mutations of KRAS are involved in many different kinds of tumors [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of acidosis on adipose-derived stem cell impairment and gene expression

Huang,

Wang,

et al. 2024

Regenerative Therapy

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“…CDC42, the protein encoded by this gene, is a small GTPase of the Rho subfamily, which regulates the signaling pathways that control diverse cellular functions, including cell morphology, migration, endocytosis, and cell cycle progression. 28 NFKBIA encodes a member of the nuclear factor (NF)-kappa-B inhibitor family, which contains multiple ankyrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes involved in inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Time‐series transcriptome analysis of peripheral blood mononuclear cells obtained from individuals who received the SARS‐CoV‐2 mRNA vaccine

Watanabe

Yamamoto

Matsuba³

et al. 2023

Journal of Medical Virology

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Messenger ribonucleic acid (mRNA) vaccination against coronavirus disease 2019 (COVID-19) is an effective prevention strategy, despite a limited understanding of the molecular mechanisms underlying the host immune system and individual heterogeneity of the variable effects of mRNA vaccination. We assessed the timeseries changes in the comprehensive gene expression profiles of 200 vaccinated healthcare workers by performing bulk transcriptome and bioinformatics analyses, including dimensionality reduction utilizing the uniform manifold approximation and projection (UMAP) technique. For these analyses, blood samples, including peripheral blood mononuclear cells (PBMCs), were collected from 214 vaccine recipients before vaccination (T1) and on Days 22 (T2, after second dose), 90, 180 (T3, before a booster dose), and 360 (T4, after a booster dose) after receiving the first dose of BNT162b2 vaccine (UMIN000043851). UMAP successfully visualized the main cluster of gene expression at each time point in PBMC samples (T1-T4).Through differentially expressed gene (DEG) analysis, we identified genes that showed fluctuating expression levels and gradual increases in expression levels from T1 to T4, as well as genes with increased expression levels at T4 alone. We also succeeded in dividing these cases into five types based on the changes in gene expression levels. High-throughput and temporal bulk RNA-based transcriptome analysis is a useful approach for inclusive, diverse, and cost-effective large-scale clinical studies.

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Role of a small GTPase Cdc42 in aging and age-related diseases

Cited by 14 publications

References 191 publications

Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia

Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia

Effect of acidosis on adipose-derived stem cell impairment and gene expression

Time‐series transcriptome analysis of peripheral blood mononuclear cells obtained from individuals who received the SARS‐CoV‐2 mRNA vaccine

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