The pathophysiology of <i>HOX</i> genes and their role in cancer

Grier, David G.; Thompson, Alexander; Kwasniewska, Alexandra; McGonigle, Glenda J.; Halliday, Henry L.; Lappin, Terence

doi:10.1002/path.1710

Cited by 291 publications

(264 citation statements)

References 144 publications

(116 reference statements)

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“…Consistent with this, gene expression profiling of samples from AML patients with t(8;16)(p11;p13) revealed a characteristic pattern of Hox gene expression, with elevated levels of HOXA9, HOXA10 and MEIS1 (Camos et al, 2006). Increased expression of these proteins has been linked to leukemia induction (Grier et al, 2005). TIF2 (transcription intermediary factor 2) is a third fusion partner identified for MOZ.…”

Section: Moz and Morf In Leukemia Leiomyomata And Other Malignanciesmentioning

confidence: 57%

“…Moreover, expression of c-kit, c-Mpl and HoxA9 is reduced. HoxA9 is a key player in hematopoiesis and leukemogenesis (Grier et al, 2005), and its nuclear localization is promoted by thrombopietin, the ligand of c-Mpl (Kirito et al, 2004). Moreover, there is a genetic interaction between c-kit and c-Mpl in repopulating hematopoietic stem cells (Antonchuk et al, 2004).…”

Section: Moz and Morf In Mouse And Zebrafish Developmentmentioning

confidence: 99%

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MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

2007

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Genes of the human monocytic leukemia zinc-finger protein MOZ (HUGO symbol, MYST3) and its paralog MORF (MYST4) are rearranged in chromosome translocations associated with acute myeloid leukemia and/or benign uterine leiomyomata. Both proteins have intrinsic histone acetyltransferase activity and are components of quartet complexes with noncatalytic subunits containing the bromodomain, plant homeodomain-linked (PHD) finger and proline-tryptophan-tryptophan-proline (PWWP)-containing domain, three types of structural modules characteristic of chromatin regulators. Although leukemia-derived fusion proteins such as MOZ-TIF2 promote self-renewal of leukemic stem cells, recent studies indicate that murine MOZ and MORF are important for proper development of hematopoietic and neurogenic progenitors, respectively, thereby highlighting the importance of epigenetic integrity in safeguarding stem cell identity.

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Section: Moz and Morf In Leukemia Leiomyomata And Other Malignanciesmentioning

confidence: 57%

Section: Moz and Morf In Mouse And Zebrafish Developmentmentioning

confidence: 99%

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

2007

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“…Spatiotemporal aberrations in HOX gene expression have been found with polycystic ovarian syndrome (PCOS), endometriosis, hydrosalpinges, and endocrine disrupters that compromise reproduction [8,29]. Moreover, there is accumulating evidence that HOX genes play important roles in oncogenesis, including ovarian cancer progression [30]. However, the specific role of HOX genes in granulosa cell function and oncogenesis has not been extensively explored.…”

Section: Discussionmentioning

confidence: 99%

“…Quantitative analysis showed the expression level of HOXA7 was significantly higher in the granulosa tumor cell line, KGN, compared to primary hGCs and SVOG cells. It has been reported that many cancers, including leukemia, colon, skin, prostate, breast and ovarian cancers, have shown alterations in the expression patterns of HOX genes [30,32]. The overexpression of HOX genes has been widely associated with a variety of ovarian carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells

Huang

Cheng

Nishi³

et al. 2010

Reprod Biol Endocrinol

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BackgroundHomeobox (HOX) genes encode transcription factors, which regulate cell proliferation, differentiation, adhesion, and migration. The deregulation of HOX genes is frequently associated with human reproductive system disorders. However, knowledge regarding the role of HOX genes in human granulosa cells is limited.MethodsTo determine the role of HOXA7 in the regulation and associated mechanisms of cell proliferation in human granulosa cells, HOXA7 and epidermal growth factor receptor (EGFR) expressions were examined in primary granulosa cells (hGCs), an immortalized human granulosa cell line, SVOG, and a granulosa tumor cell line, KGN, by real-time PCR and Western blotting. To manipulate the expression of HOXA7, the HOXA7 specific siRNA was used to knockdown HOXA7 in KGN. Conversely, HOXA7 was overexpressed in SVOG by transfection with the pcDNA3.1-HOAX7 vector. Cell proliferation was measured by the MTT assay.ResultsOur results show that HOXA7 and EGFR were overexpressed in KGN cells compared to hGCs and SVOG cells. Knockdown of HOXA7 in KGN cells significantly decreased cell proliferation and EGFR expression. Overexpression of HOXA7 in SVOG cells significantly promoted cell growth and EGFR expression. Moreover, the EGF-induced KGN proliferation was abrogated, and the activation of downstream signaling was diminished when HOXA7 was knocked down. Overexpression of HOXA7 in SVOG cells had an opposite effect.ConclusionsOur present study reveals a novel mechanistic role for HOXA7 in modulating granulosa cell proliferation via the regulation of EGFR. This finding contributes to the knowledge of the pro-proliferation effect of HOXA7 in granulosa cell growth and differentiation.

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“…In human HOX gene family, there are four clusters (A, B, C, and D) located on four different chromosomes (7p15, 17p21, 12q13, and 2q31, respectively) 4, 5. There are 39 HOX genes in HOX gene family, and these genes are assigned to 13 paralog groups in each cluster, based on the position within the cluster and the homeobox sequence similarity.…”

Section: Introductionmentioning

confidence: 99%

HOXA11 antisense long noncoding RNA (HOXA11‐AS): A promising lncRNA in human cancers

Zhou

Xie

et al. 2018

Cancer Medicine

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The cancers are the leading cause of disease‐related deaths worldwide with a high risk of morbidity and mortality. Long noncoding RNAs (lncRNAs) play a critical role in a wide range of biological processes, including tumorigenesis. HOXA11‐AS (NCRNA00076), the antisense strands of HOXA11 gene, was initially revealed in a mouse embryonic cDNA library in 2009 and it was a fairly novel lncRNA. This review summarized the advanced research progression concerning the expression and role of HOXA11‐AS in different human malignancies. The expression of HOXA11‐AS is aberrantly altered in many cancers, either as a tumor suppressor or as a tumor accelerator. The different underlying mechanism of HOXA11‐AS in different cancers (including, nonsmall cell lung cancers, osteosarcoma, uveal melanoma, glioma, hepatocellular carcinoma, gastric cancer, breast cancer, cervical cancer, ovarian cancer, colorectal cancer, ovarian cancer, and glioblastoma) was also detailed. These findings lead us to conclude that HOXA11‐AS participate in the complex network of cancers and plays an important role in the tumorigenesis and progression. Functional HOXA11‐AS could be a promising biomarker for early detection as well as prognosis evaluation in cancer patients. Future HOXA11‐AS‐targeted intervention may become a valuable novel therapeutic tool, improving the clinical management of cancers.

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The pathophysiology of HOX genes and their role in cancer

Cited by 291 publications

References 144 publications

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells

HOXA11 antisense long noncoding RNA (HOXA11‐AS): A promising lncRNA in human cancers

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