Geminin is required for Hox gene regulation to pattern the developing limb

Lewis, Emily M.A.; Sankar, Savita; Tong, Caili; Patterson, Emily S.; Waller, Laura E.; Gontarz, Paul; Zhang, Bo; Ornitz, David M.; Kroll, Kristen L.

doi:10.1016/j.ydbio.2020.05.007

Cited by 4 publications

(1 citation statement)

References 66 publications

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“…Previous studies have identified the HOX family as essential regulators not only for body segments during embryonic development, [27][28][29] but also for multiple tumor progression. Since EMT has also emerged as a critical cell behavior in the formation of body plan and initiation of tumor cell invasion, it would be reasonable to speculate that some HOX family members may engage in the comprehensive picture of EMT.…”

Section: Discussionmentioning

confidence: 99%

HOXD13 suppresses prostate cancer metastasis and BMP4‐induced epithelial‐mesenchymal transition by inhibiting SMAD1

Shangguan

Pan

et al. 2021

Intl Journal of Cancer

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The HOX genes are a group of highly conserved Homeobox-containing genes that control the body plan organization during development. However, their contributions to tumorigenesis and tumor progression remain uncertain and controversial. Here we provided evidence of tumor-suppressive activity of HOXD13 in prostate cancer.HOXD13 depletion contributes to more aggressiveness of prostate cancer cells in vitro and in vivo. These effects were corroborated in a metastatic mice model, where we observed more bone metastatic lesions formed by prostate cancer cells with HOXD13 ablation. Mechanistically, HOXD13 prevents BMP4-induced epithelialmesenchymal transition (EMT) by inhibiting mothers against decapentaplegic homolog 1 (SMAD1) transcription. Both bioinformation and our tissue microarray cohort data show that HOXD13 expression inversely correlated in advanced prostate cancer patient specimens. Our findings establish HOXD13 as a negative regulator of prostate cancer progression and metastasis by preventing BMP4/SMAD1 signaling, and potentially suggest new strategies for targeting metastatic prostate cancer.

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Section: Discussionmentioning

confidence: 99%

HOXD13 suppresses prostate cancer metastasis and BMP4‐induced epithelial‐mesenchymal transition by inhibiting SMAD1

Shangguan

Pan

et al. 2021

Intl Journal of Cancer

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MCM complex members MCM3 and MCM7 are associated with a phenotypic spectrum from Meier-Gorlin syndrome to lipodystrophy and adrenal insufficiency

et al. 2021

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The MCM2-7 helicase is a heterohexameric complex with essential roles as part of both the pre-replication and pre-initiation complexes in the early stages of DNA replication. Meier-Gorlin syndrome, a rare primordial dwarfism, is strongly associated with disruption to the pre-replication complex, including a single case described with variants in MCM5. Conversely, a biallelic pathogenic variant in MCM4 underlies immune deficiency with growth retardation, features also seen in individuals with pathogenic variants in other pre-initiation complex encoding genes such as GINS1, MCM10, and POLE. Through exome and chromium genome sequencing, supported by functional studies, we identify biallelic pathogenic variants in MCM7 and a strong candidate biallelic pathogenic variant in MCM3. We confirm variants in MCM7 are deleterious and through interfering with MCM complex formation, impact efficiency of S phase progression. The associated phenotypes are striking; one patient has typical Meier-Gorlin syndrome, whereas the second case has a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. We provide further insight into the developmental complexity of disrupted MCM function, highlighted by two patients with a similar variant profile in MCM7 but disparate clinical features. Our results build on other genetic findings linked to disruption of the pre-replication and pre-initiation complexes, and the replisome, and expand the complex clinical genetics landscape emerging due to disruption of DNA replication.

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New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis

Chen,

Shen,

Yang

et al. 2024

BMC Med Genomics

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Background Synpolydactyly (SPD) is mainly caused by mutations of polyalanine expansion (PAE) in the transcription factor gene HOXD13 and the involved cell types and signal pathway are still not clear possible pathways and single-cell expression characteristics of limb bud in HOXD13 PAE mice was analyzed in this study. Method We investigated a previous study of a mouse model with SPD and conducted weighted gene co-expression network analysis (WGCNA) using a single-cell RNA sequencing dataset from limb bud cells of SPD mouse model of HOXD13 + 7A heterozygote. Results Analysis of WGCNA revealed that synpolydactyly-associated Hoxd13 PAEs alter the immune response and osteoclast differentiation, and enhance DNA replication. Bmp4 , Hand2 , Hoxd12 , Lnp , Prrx1 , Gmnn , and Cdc6 were found to play potentially key roles in synpolydactyly. Conclusions These findings evaluated the main genes related to SPD with PAE mutations in HOXD13 and advance our understanding of human limb development. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-024-01974-9.

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Geminin is required for Hox gene regulation to pattern the developing limb

Cited by 4 publications

References 66 publications

HOXD13 suppresses prostate cancer metastasis and BMP4‐induced epithelial‐mesenchymal transition by inhibiting SMAD1

HOXD13 suppresses prostate cancer metastasis and BMP4‐induced epithelial‐mesenchymal transition by inhibiting SMAD1

MCM complex members MCM3 and MCM7 are associated with a phenotypic spectrum from Meier-Gorlin syndrome to lipodystrophy and adrenal insufficiency

New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis

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