Hox Genes and Teratogenic Factors

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

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PATH-25. SURVIVAL STRATIFICATION OF IDH MUTANT GLIOMA USING METHYLATION AND mRNA ANALYSIS OF HOX GENES

Neuro-Oncology ◽

10.1093/neuonc/noy148.681 ◽

2018 ◽

Vol 20 (suppl_6) ◽

pp. vi163-vi164

Author(s):

Yasin Mamatjan ◽

Severa Bunda ◽

Fabio Moraes ◽

Suganth Suppiah ◽

Pardeep Heir ◽

...

Keyword(s):

Hox Genes ◽

Mrna Analysis

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Hox dosage contributes to flight appendage morphology in Drosophila

Nature Communications ◽

10.1038/s41467-021-23293-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Rachel Paul ◽

Guillaume Giraud ◽

Katrin Domsch ◽

Marilyne Duffraisse ◽

Frédéric Marmigère ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Differential Expression ◽

Hox Genes ◽

Expression Profiles ◽

Fruit Fly ◽

Insect Species ◽

Wing Morphology ◽

Hox Proteins ◽

Spatial Expression ◽

Flying Insects

AbstractFlying insects have invaded all the aerial space on Earth and this astonishing radiation could not have been possible without a remarkable morphological diversification of their flight appendages. Here, we show that characteristic spatial expression profiles and levels of the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) underlie the formation of two different flight organs in the fruit fly Drosophila melanogaster. We further demonstrate that flight appendage morphology is dependent on specific Hox doses. Interestingly, we find that wing morphology from evolutionary distant four-winged insect species is also associated with a differential expression of Antp and Ubx. We propose that variation in the spatial expression profile and dosage of Hox proteins is a major determinant of flight appendage diversification in Drosophila and possibly in other insect species during evolution.

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The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML

Journal of Translational Medicine ◽

10.1186/s12967-021-02914-2 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Chao Guo ◽

Ya-yue Gao ◽

Qian-qian Ju ◽

Chun-xia Zhang ◽

Ming Gong ◽

...

Keyword(s):

Regression Analysis ◽

Prediction Model ◽

Hox Genes ◽

Expression Profiles ◽

Penalized Regression ◽

Diagnostic Utility ◽

Lasso Regression ◽

Hub Genes ◽

Npm1 Mutation ◽

Genetic Abnormalities

Abstract Background The heterogenous cytogenetic and molecular variations were harbored by AML patients, some of which are related with AML pathogenesis and clinical outcomes. We aimed to uncover the intrinsic expression profiles correlating with prognostic genetic abnormalities by WGCNA. Methods We downloaded the clinical and expression dataset from BeatAML, TCGA and GEO database. Using R (version 4.0.2) and ‘WGCNA’ package, the co-expression modules correlating with the ELN2017 prognostic markers were identified (R2 ≥ 0.4, p < 0.01). ORA detected the enriched pathways for the key co-expression modules. The patients in TCGA cohort were randomly assigned into the training set (50%) and testing set (50%). The LASSO penalized regression analysis was employed to build the prediction model, fitting OS to the expression level of hub genes by ‘glmnet’ package. Then the testing and 2 independent validation sets (GSE12417 and GSE37642) were used to validate the diagnostic utility and accuracy of the model. Results A total of 37 gene co-expression modules and 973 hub genes were identified for the BeatAML cohort. We found that 3 modules were significantly correlated with genetic markers (the ‘lightyellow’ module for NPM1 mutation, the ‘saddlebrown’ module for RUNX1 mutation, the ‘lightgreen’ module for TP53 mutation). ORA revealed that the ‘lightyellow’ module was mainly enriched in DNA-binding transcription factor activity and activation of HOX genes. The ‘saddlebrown’ module was enriched in immune response process. And the ‘lightgreen’ module was predominantly enriched in mitosis cell cycle process. The LASSO- regression analysis identified 6 genes (NFKB2, NEK9, HOXA7, APRC5L, FAM30A and LOC105371592) with non-zero coefficients. The risk score generated from the 6-gene model, was associated with ELN2017 risk stratification, relapsed disease, and prior MDS history. The 5-year AUC for the model was 0.822 and 0.824 in the training and testing sets, respectively. Moreover, the diagnostic utility of the model was robust when it was employed in 2 validation sets (5-year AUC 0.743–0.79). Conclusions We established the co-expression network signature correlated with the ELN2017 recommended prognostic genetic abnormalities in AML. The 6-gene prediction model for AML survival was developed and validated by multiple datasets.

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Hox genes are essential for the development of eyespots in Bicyclus anynana butterflies

Genetics ◽

10.1093/genetics/iyaa005 ◽

2020 ◽

Vol 217 (1) ◽

Author(s):

Yuji Matsuoka ◽

Antónia Monteiro

Keyword(s):

Hox Genes ◽

Bicyclus Anynana ◽

Hox Gene ◽

Novel Traits ◽

Anterior Posterior ◽

Anterior Posterior Axis

Abstract The eyespot patterns found on the wings of nymphalid butterflies are novel traits that originated first in hindwings and subsequently in forewings, suggesting that eyespot development might be dependent on Hox genes. Hindwings differ from forewings in the expression of Ultrabithorax (Ubx), but the function of this Hox gene in eyespot development as well as that of another Hox gene Antennapedia (Antp), expressed specifically in eyespots centers on both wings, are still unclear. We used CRISPR-Cas9 to target both genes in Bicyclus anynana butterflies. We show that Antp is essential for eyespot development on the forewings and for the differentiation of white centers and larger eyespots on hindwings, whereas Ubx is essential not only for the development of at least some hindwing eyespots but also for repressing the size of other eyespots. Additionally, Antp is essential for the development of silver scales in male wings. In summary, Antp and Ubx, in addition to their conserved roles in modifying serially homologous segments along the anterior–posterior axis of insects, have acquired a novel role in promoting the development of a new set of serial homologs, the eyespot patterns, in both forewings (Antp) and hindwings (Antp and Ubx) of B. anynana butterflies. We propose that the peculiar pattern of eyespot origins on hindwings first, followed by forewings, could be due to an initial co-option of Ubx into eyespot development followed by a later, partially redundant, co-option of Antp into the same network.

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