HOX genes function in Breast Cancer development

Garcia, Simone Aparecida de Bessa; Araújo, Mafalda; Pereira, Tiago; Mouta, J.; Freitas, Renata

doi:10.1016/j.bbcan.2020.188358

Cited by 58 publications

(68 citation statements)

References 132 publications

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“…For some HOX genes, and considering particular contexts such as embryonic development or cancer, epigenetic variations and their downstream effects are still under investigation. The human genome contains 39 genes organized into four clusters (HOXA, HOXB, HOXC and HOXD) located within distinct chromosomes (7p15, 17q21.2, 12q13, 2q31, respectively), encoding transcription factors and noncoding RNAs that are crucial for embryonic development, cellular physiology and tissue homeostasis ( Figure 3) [15,16]. A large number of studies, including genome-wide association approaches, have highlighted connections between HOX gene expression and cancer, either being downregulated or upregulated in comparison with its normal counterparts, where they may act as tumor suppressors or proto-oncogenes in a tissue-specific context [17].…”

Section: Introductionmentioning

confidence: 99%

“…These alterations in HOX gene expression could be the result of epigenetic processes that affect chromatin accessibility, or genetic processes that affect the HOX gene DNA sequence, cofactor assembly and upstream regulators. Changes in the expression profile of these genes and functional abnormalities in the encoded transcription factors have been shown to affect several cellular processes, such as angiogenesis, autophagy, proliferation, apoptosis, migration and metabolism [15,17,18]. HOX gene mutations have been investigated in the past decade and found to increase cancer susceptibility, beyond being related to limb malformations, among other physiologic disorders [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Methylation in HOX Clusters and Its Applications in Cancer Therapy

Paço¹,

Garcia

Freitas

2020

Cells

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HOX genes are commonly known for their role in embryonic development, defining the positional identity of most structures along the anterior–posterior axis. In postembryonic life, HOX gene aberrant expression can affect several processes involved in tumorigenesis such as proliferation, apoptosis, migration and invasion. Epigenetic modifications are implicated in gene expression deregulation, and it is accepted that methylation events affecting HOX gene expression play crucial roles in tumorigenesis. In fact, specific methylation profiles in the HOX gene sequence or in HOX-associated histones are recognized as potential biomarkers in several cancers, helping in the prediction of disease outcomes and adding information for decisions regarding the patient’s treatment. The methylation of some HOX genes can be associated with chemotherapy resistance, and its identification may suggest the use of other treatment options. The use of epigenetic drugs affecting generalized or specific DNA methylation profiles, an approach that now deserves much attention, seems likely to be a promising weapon in cancer therapy in the near future. In this review, we summarize these topics, focusing particularly on how the regulation of epigenetic processes may be used in cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Methylation in HOX Clusters and Its Applications in Cancer Therapy

Paço¹,

Garcia

Freitas

2020

Cells

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“…The HOX gene family is highly conserved across species; according to the distribution of the HOX gene family in different chromosomes, four subgroups with genomic clusters of A-D were established (6,7). Primarily, the HOX gene family drives normal cellular differentiation and morphogenesis in embryonic stages, and regulates normal tissue morphology in adults (8).…”

Section: Introductionmentioning

confidence: 99%

Low HOXC10 expression in liver cancer regulates proliferation via a mechanism involving miR‑221 and the MAPK signaling pathway

Zhao

Guo

et al. 2020

Oncol Lett

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Homeodomain-containing gene 10 (HOXC10) is associated with the progression of a variety of different types of human cancer; however, the role of HOXC10 in liver cancer is not completely understood. The present study aimed to investigate the mechanisms underlying the effects of HOXC10 on liver cancer tumorigenesis. Quantitative PCR and western blotting were used to detect the expression patterns of HOXC10 in cancer and adjacent healthy tissues. EdU, Cell Counting Kit-8 and colony formation assays were used to determine the functions of HOXC10 in liver cancer cell lines. ENCORI, TargetScan and miRTarBase were used to identify microRNAs that target HOXC10. The verification of the interaction between HOXC10 and microRNA-221 was determined by a luciferase assay. Compared with adjacent non-cancerous tissues, the expression of HOXC10 was markedly decreased in liver cancer tissues. A HOXC10 small interfering (si)RNA significantly attenuated HOXC10 expression at the mRNA and protein levels, and enhanced cell proliferation compared with the siRNA-negative control group. In addition, the luciferase reporter assay indicated that microRNA-221 directly bound to the 3'-untranslated region of HOXC10, and interfered with the inhibitory effect of HOXC10 on proliferation. In addition, HOXC10 knockdown elevated the expression levels of mitogen-activated protein kinase signaling pathway markers compared with the siRNA-negative control group. Therefore, the results of the present study may aid with the development of novel therapeutic regimens and diagnostic markers of liver cancer.

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“…Increasing number of HOX proteins have been investigated in various tumors, including acute myeloid leukemia (5), breast cancer (6), lung cancer (7), digestive tract neoplasms (8)(9)(10), and so on. Currently, diverse HOX proteins have been reported to be implicated in the carcinogenesis and development of GC.…”

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Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

Jin

Dai

et al. 2020

Preprint

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Background Increasing studies have uncovered aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and potential acting mechanisms of HOX proteins in GC.Methods A comprehensive search on PubMed, Embase, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) and the pooled odds ratio (OR) with its 95% CI were used to assess the effect of HOX proteins expression on the prognosis and clinicopathological features of GC, respectively.Results A total of 19 studies involving 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I2 = 90.5%, p = 0.000). The subgroup analysis showed that elevated expression of HOX proteins in the down-regulated subgroup was associated with a good prognosis in GC. (pooled HR: 0.46, 95% CI: 0.36–0.59, I2 = 3.1%, p = 0.377), while over-expressed HOX proteins in the up-regulated subgroup were related to poor OS. (pooled HR: 2.59, 95% CI: 1.79–3.74, I2 = 73.5%, p = 0.000). The aberrant expression of HOX proteins was crucially related to the TNM stage, depth of tumor invasion, tumor size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in GC. In addition, the molecular mechanisms how HOX proteins regulate tumorigenesis and development of GC were also explored.Conclusions HOX proteins play vital roles in GC progression and might serve as prognostic markers for GC. Novel therapeutic strategies targeting HOX proteins might be promising for GC prevention and therapy.

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HOX genes function in Breast Cancer development

Cited by 58 publications

References 132 publications

Methylation in HOX Clusters and Its Applications in Cancer Therapy

Methylation in HOX Clusters and Its Applications in Cancer Therapy

Low HOXC10 expression in liver cancer regulates proliferation via a mechanism involving miR‑221 and the MAPK signaling pathway

Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

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