Cervical cancer-associated promoter polymorphism affects akna expression levels

Martínez‐Nava, Gabriela Angélica; Torres-Poveda, Kirvis; Lagunas‐Martínez, Alfredo; Bahena-Román, Margarita; Zurita-Díaz, M A; Ortíz-Flores, E; García‐Carrancá, Alejandro; Madrid‐Marina, Vicente; Burguete-García, Ana I.

doi:10.1038/gene.2014.60

Cited by 7 publications

(10 citation statements)

References 47 publications

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“…Recent findings, suggest that the AT-hook transcriptional factor AKNA, could play a role in the development of CC [6]. This gene is located on chromosome 9q32, a locus of genetic susceptibility to CC [7].…”

Section: Introductionmentioning

confidence: 99%

The Human Papillomavirus (HPV) E6 Oncoprotein Regulates CD40 Expression via the AT-Hook Transcription Factor AKNA

Manzo-Merino

Lagunas‐Martínez

Contreras-Ochoa

et al. 2018

Cancers

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Persistent infection with high-risk Human Papillomavirus (HR-HPV) is the main requisite for cervical cancer development. Normally, HPV is limited to the site of infection and regulates a plethora of cellular elements to avoid the immune surveillance by inducing an anti-inflammatory state, allowing the progress through the viral cycle and the carcinogenic process. Recent findings suggest that the AT-hook transcriptional factor AKNA could play a role in the development of cervical cancer. AKNA is strongly related to the expression of co-stimulatory molecules such CD40/CD40L to achieve an anti-tumoral immune response. To date, there is no evidence demonstrating the effect of the HPV E6 oncoprotein on the AT-hook factor AKNA. In this work, minimal expression of AKNA in cervical carcinoma compared to normal tissue was found. We show the ability of E6 from high-risk HPVs 16 and 18 to interact with and down-regulate AKNA as well as its co-stimulatory molecule CD40 in a proteasome dependent manner. We also found that p53 interacts with AKNA and promotes AKNA expression. Our results indicate that the de-regulation of CD40 and AKNA is induced by the HPV E6 oncoprotein, and this event involves the action of p53 suggesting that the axis E6/p53A/AKNA might play an important role in the de-regulation of the immune system during the carcinogenic process induced by HR-HPV.

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Section: Introductionmentioning

confidence: 99%

The Human Papillomavirus (HPV) E6 Oncoprotein Regulates CD40 Expression via the AT-Hook Transcription Factor AKNA

Manzo-Merino

Lagunas‐Martínez

Contreras-Ochoa

et al. 2018

Cancers

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“…Previous studies have revealed the crucial functions of AKNA in multiple physiological and pathological processes such as development, immune function, inflammation, and cancer [5,21,22]. However, the role of AKNA in GC is not yet clear.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidences indicated crucial function of AKNA might exert in multiple cancers. In cervical cancer, single-nucleotide polymorphisms (SNPs) make AKNA a susceptibility genetic factor [5]. AKNA directly binds the A/T-rich promoters regions of CD40 and CD40 ligand (CD40L) and coordinately regulates their expression, thereby activate antitumor immune response, while HPV E6, a cervical cancer-related oncoprotein, could downregulate AKNA and lead to the progression of cancer [6,7].…”

Section: Introductionmentioning

confidence: 99%

AKNA Is a Potential Prognostic Biomarker in Gastric Cancer and Function as a Tumor Suppressor by Modulating EMT-Related Pathways

Wang

Sun

2020

BioMed Research International

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The AT-hook transcription factor, AKNA, is a nuclear protein that affects a few physiological and pathological processes including cancer. Here, we investigated the role of AKNA in gastric cancer (GC). By using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, AKNA was found deregulated in both GC cell lines and 32 paired GC tissues. Subsequently, Kaplan-Meier analysis and clinicopathological analysis were conducted using both 32 GC cases’ data above and RNA-Seq data of AKNA in 354 GC patients and the corresponding clinical-pathological data obtained from The Cancer Genome Atlas (TCGA), and AKNA expression was found closely related to location, metastasis, and TNM staging of GC. Then, the potential molecular mechanisms of AKNA in GC were explored by gene set enrichment analysis (GSEA), qRT-PCR, and Western blot assays. AKNA was found to be a hub gene related to homotypic cell to cell adhesion, regulation of cell to cell adhesion, leukocyte cell to cell adhesion, and regulation of T cell proliferation in GC. GO analysis revealed that AKNA involved in the regulation of epithelial-mesenchymal transition (EMT)-related pathways including chemokine signaling pathway, cytokine to cytokine receptor interaction, cell adhesion molecules, and jak-stat signaling pathway in GC. To explore the regulation of AKNA expression, Targetscan and TargetMiner were used to predict the possible miRNA which targeted AKNA and found the expression of AKNA was negatively correlated to miR-762 which could be sponged by circTRNC18. In conclusion, AKNA could function as a tumor suppressor by modulating EMT-related pathways in GC. The expression of AKNA might be regulated by circTRNC18/miR-762 axis. AKNA could serve as a potential biomarker and an effective target for GC diagnosis and therapy.

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“…This polymorphism has been proposed as an expression quantitative trait loci (eQTL), given that in peripheral blood mononuclear cells the A allele promotes higher expression level of AKNA [14]. …”

Section: Discussionmentioning

confidence: 99%

“…Particularly, AKNA upregulates the expression of two costimulatory molecules, CD40 and CD40L, in T and B-lymphocytes, as well as natural killer and dendritic cells [13]. To date, AKNA gene polymorphisms as well as its expression had been associated with other human pathologies in which the immune system plays an important role such as cervical cancer [14], leukemia [15], Vogt-Koyanagi-Harada's syndrome [16], and hepatitis C virus infection [17]. …”

Section: Introductionmentioning

confidence: 99%

HIF1A(rs11549465) andAKNA(rs10817595) Gene Polymorphisms Are Associated with Primary Sjögren’s Syndrome

Hernández-Molina

Rodríguez-Pérez

Fernández‐Torres

et al. 2017

BioMed Research International

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Objective. To evaluate the allele and genotype frequencies of polymorphic sites of HIF1A and ANKA genes in primary Sjögren's syndrome (pSS). Methods. We included 110 patients with pSS and 141 ethnically matched healthy controls. Three HIF1A gene polymorphisms (Pro582Ser, Ala588Thr, and C191T) and two AKNA gene polymorphisms (−1372C>A and Pro624Leu) were genotyped using TaqMan probes in a Real-Time PCR instrument. Associations between pSS and genotypes, alleles, and inheritance models of the SNPs of interest were evaluated by logistic regression adjusted by age and gender. Results. The C/T genotype and the T allele of the HIF1A Pro582Ser polymorphism protected against pSS (OR = 0.22; 95% CI = 0.09–0.52; P < 0.01; OR = 0.26; 95% CI = 0.12–0.58; P < 0.01, resp.), whereas under a recessive model adjusted by age and gender, the AKNA −1372C>A polymorphism A/A genotype was associated with an increased risk of pSS (OR = 2.60; 95% CI = 1.11–6.12; P = 0.03). Conclusions. We identified HIF1A Pro582Ser T allele and C/T genotype as well as AKNA −1372C>A polymorphism A/A genotype as genetic factors associated with pSS. Further studies in other populations are needed to validate our findings and research is warranted in order to shed some light on their functional implications across biological pathways in this disease.

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Cervical cancer-associated promoter polymorphism affects akna expression levels

Cited by 7 publications

References 47 publications

The Human Papillomavirus (HPV) E6 Oncoprotein Regulates CD40 Expression via the AT-Hook Transcription Factor AKNA

The Human Papillomavirus (HPV) E6 Oncoprotein Regulates CD40 Expression via the AT-Hook Transcription Factor AKNA

AKNA Is a Potential Prognostic Biomarker in Gastric Cancer and Function as a Tumor Suppressor by Modulating EMT-Related Pathways

HIF1A(rs11549465) andAKNA(rs10817595) Gene Polymorphisms Are Associated with Primary Sjögren’s Syndrome

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