HOX Genes as Potential Markers of Circulating Tumour Cells

Morgan, Richard; El‐Tanani, Mohamed

doi:10.2174/1566524016666160316145715

Cited by 17 publications

(14 citation statements)

References 47 publications

(50 reference statements)

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“…The differential expression of HOX genes in cancer make the products of these genes potential biomarkers for both diagnosis and prognosis, and for precision medicine applications such as predicting treatment response (reviewed by Morgan and El-Tanani, 2016 [ 36 ]). One of the best characterized examples is Engrailed-2 ( EN2 ), a gene that is very closely related to the HOX genes but which is not located within the 4 main chromosomal clusters described above [ 37 ].…”

Section: Hox Genes In Cancermentioning

confidence: 99%

“…HOX gene expression at the RNA level has also been shown to have prognostic significance in acute myeloid leukaemia (AML) [ 41 ], and in several solid malignancies including mesothelioma (HOXB4) [ 42 ], breast cancer (HOXB7) [ 43 ], ovarian cancer [ 44 ], oral squamous cell carcinoma (HOXD13) [ 45 ], thyroid cancer (HOXC10) [ 46 ], clear cell renal cell carcinoma (HOXC11) [ 47 ], gastric cancer (HOXC6) [ 48 ], and bladder cancer (HOXB13) [ 49 ]. Discreet patterns of HOX gene expression apparently exist within different types of cancer, indicating that they could be used to distinguish between cancer types when the primary tumour type is unknown, for example in circulating tumour cells (CTCs) [ 36 ].…”

Section: Hox Genes In Cancermentioning

confidence: 99%

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Targeting HOX/PBX dimers in cancer

et al. 2017

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The HOX and PBX gene families encode transcription factors that have key roles in establishing the identity of cells and tissues in early development. Over the last 20 years it has become apparent that they are also dysregulated in a wide range of solid and haematological malignancies and have a predominantly pro-oncogenic function. A key mode of transcriptional regulation by HOX and PBX proteins is through their interaction as a heterodimer or larger complex that enhances their binding affinity and specificity for DNA, and there is growing evidence that this interaction is a potential therapeutic target in malignancies that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma, and acute myeloid leukaemia. This review summarizes the roles of HOX and PBX genes in cancer and assesses the therapeutic potential of HOX/PBX dimer inhibition, including the availability of biomarkers for its application in precision medicine.

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Section: Hox Genes In Cancermentioning

confidence: 99%

Section: Hox Genes In Cancermentioning

confidence: 99%

Targeting HOX/PBX dimers in cancer

et al. 2017

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“…Homeobox-containing genes are highly evolutionarily conserved; proteins encoded by homeobox-containing genes are important transcription factors that precisely regulate the differentiation of cells by specifically activating downstream genes (9,10). Studies have indicated that homeobox-containing genes serve key roles in the generation and differentiation of embryos and organs of organisms.…”

Section: Introductionmentioning

confidence: 99%

Expression of engrailed homeobox 2 regulates the proliferation, migration and invasion of non‑small cell lung cancer cells

Lin

Liu

Gong³

2018

Oncol Lett

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The present study aimed to investigate the expression, biological function and mechanism of action of engrailed homeobox 2 (EN2) in non-small cell lung cancer (NSCLC) at the tissue and cellular level. A total of 42 patients who underwent surgical resection of NSCLC tissues between January 2014 and January 2015 were included in the present study. EN2 mRNA expression levels in explanted NSCLC tissues were determined using reverse-transcription quantitative polymerase chain reaction analysis. Adenocarcinoma human alveolar basal epithelial A549 cells were transfected with negative control plasmids or those containing EN2, enabling its overexpression. To assess the effect of EN2 overexpression in A549 cells, a Cell Counting kit-8 assay was used to analyze cellular proliferation, a Transwell assay was used to evaluate cellular migration and invasion and flow cytometry was used to detect the cell cycle distribution. To measure protein expression of EN2 and β-catenin in A549 cells, western blotting was also conducted. EN2 mRNA expression levels in NSCLC tissues were lower than those in normal tissues, and were associated with metastasis, clinical staging and differentiation degrees of NSCLC. Increased expression of EN2 inhibited the proliferation of A549 cells , and suppressed their migration and invasion. Elevated EN2 expression inhibited the proliferation of A549 cells by regulating the G/S phase transition. β-catenin protein expression levels and nuclear translocation in A549 cells were inhibited by EN2 overexpression. The present study demonstrated that expression of EN2 in NSCLC tissues was downregulated and negatively associated with the degree of disease differentiation, lymphatic metastasis and clinical staging. Overexpression of EN2 inhibits the proliferation, migration and invasion of A549 cells, as well as the expression of β-Catenin and nuclear translocation.

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“…Previous studies have revealed that dysregulated HOX genes could cause abnormalities in the development and tissue formation, leading to cell malignant transformation and tumorigenesis 13 . Recent studies suggested that HOX family proteins could be used as biomarkers of circulating tumor cells 14 . The Homo sapiens HOXC10 is located on the chromosome 12, which was reported to relate with the development of various tumors including GC 15‐19 .…”

Section: Introductionmentioning

confidence: 99%

MiR‐129‐5p induces cell cycle arrest through modulating HOXC10/Cyclin D1 to inhibit gastric cancer progression

Lin

et al. 2020

FASEB j.

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MicroRNAs (miRNAs) play important roles in posttranscriptional regulation and may serve as targets for the diagnosis and treatment of cancers. Nevertheless, a comprehensive understanding of miRNAs profiles in gastric cancer progression is still lacking. Here, we report that miR‐129‐5p is downregulated in gastric cancer by analyzing TCGA database (n = 41) and clinical tumor samples (n = 60). MiR‐129‐5p transfection suppressed gastric cancer cell proliferation through inducing G1 phase arrest in vitro and inhibit xenograft tumor growth in vivo. MiR‐129‐5p directly targeted the 3′ untranslated regions (3′ UTR) of HOXC10 mRNA and downregulated its expression. Importantly, miR‐129‐5p could reverse the oncogenic effect induced by HOXC10. We systemically screened the downstream target of HOXC10 by ChIP sequencing, and found that HOXC10 could transcriptionally regulate the expression of Cyclin D1 and facilitate G1/S cell cycle transition. Notably, high levels of HOXC10 and Cyclin D1 were related with poor prognosis of gastric cancer patients (n = 90). These findings reveal a novel role of miR‐129‐5p/HOXC10/Cyclin D1 axis in modulating cell cycle and gastric tumorigenesis, which might provide potential prognostic biomarkers and therapeutic targets for gastric cancer patients.

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HOX Genes as Potential Markers of Circulating Tumour Cells

Cited by 17 publications

References 47 publications

Targeting HOX/PBX dimers in cancer

Targeting HOX/PBX dimers in cancer

Expression of engrailed homeobox 2 regulates the proliferation, migration and invasion of non‑small cell lung cancer cells

MiR‐129‐5p induces cell cycle arrest through modulating HOXC10/Cyclin D1 to inhibit gastric cancer progression

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