Low expression of ZHX1 and ZHX2 impacts on the prognosis of chronic lymphocytic leukemia

Maciel, Natália Ioseph Gladistone; Filiú-Braga, Luma Dayane Carvalho; Neves, Francisco Assis Rocha; Rego, Eduardo Magalhães; Lucena-Araújo, Antonio R.; Saldanha-Araújo, Felipe

doi:10.1186/s40364-021-00263-2

Cited by 7 publications

(4 citation statements)

References 11 publications

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“…Studies in hepatocarcinoma cells reported that ZBTB7A may regulate neural development [104], while Zou et al described Zc3h8 as a repressor of inflammation in zebrafish [105]. ZHX1 and ZHX2 participate in the development and progression of several types of cancer, and the low expression of both impacts a poor prognosis in chronic lymphocytic leukemia [106].…”

Section: Discussionmentioning

confidence: 99%

An integrated approach to identifying sex-specific genes, transcription factors, and pathways relevant to Alzheimer’s disease

López-Cerdán,

Andreu,

Hidalgo

et al. 2023

Preprint

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Background: Age is one of the bigger risk factors for developing Alzheimer's disease (AD). Still, in the last decade, several experimental studies and reviews document the role of sex in several features of AD. Understanding the impact of sex in specific molecular mechanisms in this disease is critical for tailored interventions. Methods: To explore sex differences impact disease (SDID) in AD, we conduct a systematic review during 2021 to select transcriptomic studies of AD with sex information data in public repositories in the 2002-2021 period. We focus on the main brain regions affected by AD; cortex (CT) and hippocampus (HP). Then, a differential expression analysis for each study and two tissue-specific meta-analyses were performed. Last, focusing on the cortex, where significant SDID were detected, we conducted a functional characterization: protein-protein network interaction (PPI), Over-Representation Analysis (ORA) to explore biological processes and pathways, and a VIPER analysis to estimate transcription factor activity. Results: A group of eight studies in CT and five in HP were selected from Gene Expression Omnibus (GEO) repository, for tissue-specific meta-analyses. We detected 389 significant SDID genes in CT. In general, females show more affected genes than males and the genes were grouped in six subsets according to the expression profile in females and males with AD. Only subset I (repressed genes in affected females) displayed significant results at functional profiling. Females.AD compared to males. AD showed a more significant impairment in biological processes related to the regulation and organization of synapsis, the pathways more impaired those linked to neurotransmitters (Glutamate and GABA) and several pathways related to protein folding, Abeta aggregation, and accumulation. This could explain, in part, why the cognitive decline is more pronounced in females.AD. Finally, we detected 23 TFs having different activation patterns by sex, some of them associated with AD for the first time. All results generated during this study are readily available through an open web resource. Conclusion: Our meta-analyses indicate differences in several mechanisms involved in AD between females and males. Such sex differences represent the base of new hypotheses and could importantly impact precision medicine, and improve diagnosis and clinical outcomes in AD for females and males.

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Section: Discussionmentioning

confidence: 99%

An integrated approach to identifying sex-specific genes, transcription factors, and pathways relevant to Alzheimer’s disease

López-Cerdán,

Andreu,

Hidalgo

et al. 2023

Preprint

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“…In contrast to females, unique transcription factors regulators of switch genes from M-AD and M-asymAD were predominantly associated with cancers. For example, ZHX1, a unique transcription factor in M-AD, has been implicated in gastric cancer, chronic lymphocytic leukemia, and gliomas ( Ge and Li, 2020 ; You et al, 2020 ; Maciel et al, 2021 ). TCF7 is involved in prostate cancer ( Chen et al, 2015 ; Siu et al, 2017 ), and it is highly expressed in immune cells in atherosclerosis plaques ( Ma et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Sex-specific transcriptional rewiring in the brain of Alzheimer’s disease patients

Santiago¹,

Quinn²,

Potashkin

2022

Front. Aging Neurosci.

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Sex-specific differences may contribute to Alzheimer’s disease (AD) development. AD is more prevalent in women worldwide, and female sex has been suggested as a disease risk factor. Nevertheless, the molecular mechanisms underlying sex-biased differences in AD remain poorly characterized. To this end, we analyzed the transcriptional changes in the entorhinal cortex of symptomatic and asymptomatic AD patients stratified by sex. Co-expression network analysis implemented by SWItchMiner software identified sex-specific signatures of switch genes responsible for drastic transcriptional changes in the brain of AD and asymptomatic AD individuals. Pathway analysis of the switch genes revealed that morphine addiction, retrograde endocannabinoid signaling, and autophagy are associated with both females with AD (F-AD) and males with (M-AD). In contrast, nicotine addiction, cell adhesion molecules, oxytocin signaling, adipocytokine signaling, prolactin signaling, and alcoholism are uniquely associated with M-AD. Similarly, some of the unique pathways associated with F-AD switch genes are viral myocarditis, Hippo signaling pathway, endometrial cancer, insulin signaling, and PI3K-AKT signaling. Together these results reveal that there are many sex-specific pathways that may lead to AD. Approximately 20–30% of the elderly have an accumulation of amyloid beta in the brain, but show no cognitive deficit. Asymptomatic females (F-asymAD) and males (M-asymAD) both shared dysregulation of endocytosis. In contrast, pathways uniquely associated with F-asymAD switch genes are insulin secretion, progesterone-mediated oocyte maturation, axon guidance, renal cell carcinoma, and ErbB signaling pathway. Similarly, pathways uniquely associated with M-asymAD switch genes are fluid shear stress and atherosclerosis, FcγR mediated phagocytosis, and proteoglycans in cancer. These results reveal for the first time unique pathways associated with either disease progression or cognitive resilience in asymptomatic individuals. Additionally, we identified numerous sex-specific transcription factors and potential neurotoxic chemicals that may be involved in the pathogenesis of AD. Together these results reveal likely molecular drivers of sex differences in the brain of AD patients. Future molecular studies dissecting the functional role of these switch genes in driving sex differences in AD are warranted.

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“…The prognostic impact of ZHX1 and ZHX2 in chronic lymphocytic leukemia (CLL) has recently been reported [ 34 ]. CLL patients with reduced ZHX1 and ZHX2 expression have a worse prognosis.…”

Section: Oncogenic or Tumor-suppressive Functions Of Zhxs In Cancersmentioning

confidence: 99%

Zinc Fingers and Homeobox Family in Cancer: A Double-Edged Sword

Bao

Zhang

Han

et al. 2022

IJMS

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The zinc fingers and homeobox (ZHX) family includes ZHX1, ZHX2, and ZHX3, and their proteins have similar unique structures, containing two C2H2-type zinc finger motifs and four or five HOX-like homeodomains. The members of the ZHX family can form homodimers or heterodimers with each other or with a subunit of nuclear factor Y. Previous studies have suggested that ZHXs can function as positive or negative transcriptional regulators. Recent studies have further revealed their biological functions and underlying mechanisms in cancers. This review summarized the advances of ZHX-mediated functions, including tumor-suppressive and oncogenic functions in cancer formation and progression, the molecular mechanisms, and regulatory functions, such as cancer cell proliferation, migration, invasion, and metastasis. Moreover, the differential expression levels and their association with good or poor outcomes in patients with various malignancies and differential responses to chemotherapy exert opposite functions of oncogene or tumor suppressors. Therefore, the ZHXs act as a double-edged sword in cancers.

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Low expression of ZHX1 and ZHX2 impacts on the prognosis of chronic lymphocytic leukemia

Cited by 7 publications

References 11 publications

An integrated approach to identifying sex-specific genes, transcription factors, and pathways relevant to Alzheimer’s disease

An integrated approach to identifying sex-specific genes, transcription factors, and pathways relevant to Alzheimer’s disease

Sex-specific transcriptional rewiring in the brain of Alzheimer’s disease patients

Zinc Fingers and Homeobox Family in Cancer: A Double-Edged Sword

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