Knockdown of HOXA5 inhibits the tumorigenesis in esophageal squamous cell cancer

Zhang, Hui; Zhao, Jianghai; Suo, Zhimin

doi:10.1016/j.biopha.2016.12.012

Cited by 22 publications

(12 citation statements)

References 18 publications

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“…The upregulation of CEBPB-CLDN4 signaling caused the migration and invasion of cancer cell [41]. Homeobox A5 (HOXA5) is a member of the homeobox (HOX) family and is upregulated in many types of tumors [42]. Forkhead box L1 (FOXL1) is a member of the Forkhead box (FOX) superfamily and was reported to be dysregulated in various types of cancers.…”

Section: Discussionmentioning

confidence: 99%

Genetic variability, phylogeny and functional implication of the long control region in human papillomavirus type 16, 18 and 58 in Chengdu, China

Fang

Lin

Yang

et al. 2020

Virol J

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Background: Long control region (LCR) of human papillomavirus (HPV) has shown multiple functions on regulating viral transcription. The variations of LCR related to different lineages/sub-lineages have been found to affect viral persistence and cervical cancer progression differently. In this study, we focused on gene polymorphism of HPV16/ 18/58 LCR to assess the effect variations caused on transcription factor binding sites (TFBS) and provided more data for further study of LCR in Southwest China. Methods: LCR of HPV16/18/58 were amplified and sequenced to do polymorphic and phylogenetic anlysis. Sequences of each type were aligned with the reference sequence by MEGA 6.0 to identify SNPs. Neighbor-joining phylogenetic trees were constructed using MEGA 6.0. Transcription factor binding sites were predicted by JASPAR database. Results: The prevalence of these three HPVs ranked as HPV16 (12.8%) > HPV58 (12.6%) > HPV18 (3.5%) in Chengdu, Southwest China. 59 SNPs were identified in HPV16-LCR, 18 of them were novel mutations. 30 SNP were found in HPV18-LCR, 8 of them were novel. 55 SNPs were detected in HPV58-LCR, 18 of them were novel. Also, an insertion (CTTGTCAGTTTC) was detected in HPV58-LCR between position 7279 and 7280. As shown in the neighbor-joining phylogenetic trees, most isolates of HPV16/18/58 were clustered into lineage A. In addition, one isolate of HPV16 was classified into lineage C and 3 isolates of HPV58 were classified as lineage B. JASPAR results suggested that TFBS were potentially influenced by 7/6 mutations on LCR of HPV16/18. The insertion and 5 mutations were shown effects in LCR of HPV58. Conclusion: This study provides more data for understanding the relation among LCR mutations, lineages and carcinogenesis. It also helps performing further study to demonstrate biological function of LCR and find potential marker for diagnosis and therapy.

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Section: Discussionmentioning

confidence: 99%

Genetic variability, phylogeny and functional implication of the long control region in human papillomavirus type 16, 18 and 58 in Chengdu, China

Fang

Lin

Yang

et al. 2020

Virol J

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“…Studies have demonstrated that HOXA5 plays a significant role in tumor development. The heterotopic expression of HOXA5 was found to promote the proliferation and differentiation of esophageal cancer (31). Zhang et al demonstrated that HOXA5 could constrain cell proliferation via modulating p21 in non-small cell lung cancer (32).…”

Section: Discussionmentioning

confidence: 99%

HOXA5 inhibits the proliferation and induces the apoptosis of cervical cancer cells via regulation of protein kinase B and p27

Wang

2018

Oncol Rep

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Homeobox A5 (HOXA5) is a member of the homeobox gene (HOX) family, which plays an important role in the development of various malignant tumors. Here, we speculated that HOXA5 has an effect on cervical cancer development. In our study, we aimed to explore the role and molecular mechanism of HOXA5 in regards to the cell proliferation and apoptosis in cervical cancer. We found that expression levels of HOXA5 measured by RT-qPCR and western blot assays in cervical cancer cell lines and tissues were both significantly downregulated. We performed a gain-of-function experiment by the transfection with pcDNA.3.1-HOXA5 in ME-180 and HT-3 cells to overexpress HOXA5, and the caspase-3 activity measured by caspase-3 activity assay kit and cell apoptosis detected by flow cytometry were obviously promoted. Meanwhile, cell proliferation tested by BrdU assay, invasion determined by Transwell and cell viability tested by MTT were inhibited. Moreover, protein kinase B (AKT) was activated by incubation with SC79 (AKT activator; 1 µg/ml) after HOXA5 overexpression, and reversed the effect of HOXA5 overexpression on p27 expression. Additionally, significant elevation of AKT activation measured by western blot analysis abrogated the effect of HOXA5 on caspase-3 activity, cell apoptosis, proliferation, invasion and cell viability. Taken together, this study revealed that HOXA5 inhibits cervical cancer progression by regulating AKT/p27, proposing the potential role of HOXA5 in the prevention and treatment of cervical cancer.

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“…Strikingly, very few candidate target genes are components or essential regulators of the Wnt/β-catenin, FGF, and TGF-β/Activin/BMP signaling pathways that have been identified as downstream pathways of several HOX proteins in embryonic development, neural differentiation and tumorigenesis ( Chen et al, 2005 ; Schiedlmeier et al, 2007 ; Bami et al, 2011 ; Makki and Capecchi, 2011 ; Donaldson et al, 2012 ; Carroll and Capecchi, 2015 ; Duan et al, 2015 ; Hrycaj et al, 2015 ; Roux et al, 2015 ; Karmakar et al, 2017 ; Zhang et al, 2017 ). Moreover, except from Pcp2 (see Supplementary Table S3 , line 17), none of the already identified direct or indirect targets of HOXA5 was significantly downregulated in our analysis (e.g., Ptn, Fslt1 ) ( Sanlioglu et al, 1998 ; Chen et al, 2005 ; Boucherat et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Conditional Loss of Hoxa5 Function Early after Birth Impacts on Expression of Genes with Synaptic Function

Lizen

Moens

Mouheiche

et al. 2017

Front. Mol. Neurosci.

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Hoxa5 is a member of the Hox gene family that plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. In the mouse, Hoxa5 was recently shown to be expressed in the medulla oblongata and the pons from fetal stages to adulthood. In these territories, Hoxa5 transcripts are enriched in many precerebellar neurons and several nuclei involved in autonomic functions, while the HOXA5 protein is detected mainly in glutamatergic and GABAergic neurons. However, whether HOXA5 is functionally required in these neurons after birth remains unknown. As a first approach to tackle this question, we aimed at determining the molecular programs downstream of the HOXA5 transcription factor in the context of the postnatal brainstem. A comparative transcriptomic analysis was performed in combination with gene expression localization, using a conditional postnatal Hoxa5 loss-of-function mouse model. After inactivation of Hoxa5 at postnatal days (P)1–P4, we established the transcriptome of the brainstem from P21 Hoxa5 conditional mutants using RNA-Seq analysis. One major finding was the downregulation of several genes associated with synaptic function in Hoxa5 mutant specimens including different actors involved in glutamatergic synapse, calcium signaling pathway, and GABAergic synapse. Data were confirmed and extended by reverse transcription quantitative polymerase chain reaction analysis, and the expression of several HOXA5 candidate targets was shown to co-localize with Hoxa5 transcripts in precerebellar nuclei. Together, these new results revealed that HOXA5, through the regulation of key actors of the glutamatergic/GABAergic synapses and calcium signaling, might be involved in synaptogenesis, synaptic transmission, and synaptic plasticity of the cortico-ponto-cerebellar circuitry in the postnatal brainstem.

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Knockdown of HOXA5 inhibits the tumorigenesis in esophageal squamous cell cancer

Cited by 22 publications

References 18 publications

Genetic variability, phylogeny and functional implication of the long control region in human papillomavirus type 16, 18 and 58 in Chengdu, China

Genetic variability, phylogeny and functional implication of the long control region in human papillomavirus type 16, 18 and 58 in Chengdu, China

HOXA5 inhibits the proliferation and induces the apoptosis of cervical cancer cells via regulation of protein kinase B and p27

Conditional Loss of Hoxa5 Function Early after Birth Impacts on Expression of Genes with Synaptic Function

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