Treatment With Selumetinib for Café-au-Lait Macules and Plexiform Neurofibroma in Pediatric Patients With Neurofibromatosis Type 1.

This case report describes 4 patients with a rare autosomal dominant multisystem disorder resulting from NF1 variants that leads to café-au-lait macules and neurofibromas.

Chronic Interferon Stimulated Gene Transcription Promotes Oncogene Induced Breast Cancer.

The Mre11 complex (comprising Mre11, Rad50, Nbs1) is integral to the maintenance of genome stability. We previously showed that a hypomorphic Mre11 mutant mouse strain ( Mre11 ATLD1/ATLD1 ) was highly susceptible to oncogene induced breast cancer. Here we used a mammary organoid system to examine which Mre11 dependent responses are tumor suppressive. We found that Mre11 ATLD1/ATLD1 organoids exhibited an elevated interferon stimulated gene (ISG) signature and sustained changes in chromatin accessibility. This Mre11 ATLD1/ATLD1 phenotype depended on DNA binding of a nuclear innate immune sensor, IFI205. Ablation of Ifi205 in Mre11 ATLD1/ATLD1 organoids restored baseline and oncogene-induced chromatin accessibility patterns to those observed in WT . Implantation of Mre11 ATLD1/ATLD1 organoids and activation of oncogene led to aggressive metastatic breast cancer. This outcome was reversed in implanted Ifi205 -/- Mre11 ATLD1/ATLD1 organoids. These data reveal a connection between innate immune signaling and tumor suppression in mammary epithelium. Given the abundance of aberrant DNA structures that arise in the context of genome instability syndromes, the data further suggest that cancer predisposition in those contexts may be partially attributable to tonic innate immune transcriptional programs.

GWAS of Chronic Spontaneous Urticaria Reveals Genetic Overlap with Autoimmune Diseases, Not Atopic Diseases.

Although chronic spontaneous urticaria (CSU) is a common disease, GWASs of CSU are lacking. We aimed to identify susceptibility SNPs by performing a GWAS in Chinese Han adults with CSU. The discovery cohort included 430 CSU cases and 482 healthy controls. The GWAS findings were validated in 800 CSU cases and 900 healthy controls. Genetic, functional enrichment, and bioinformatic analyses of genome-wide significant SNPs were performed to assess the association between CSU and autoimmunity or atopy. Five genome-wide significant SNPs were identified: rs434124/LILRA3, rs61986182/IGHG1/2, rs73075571/TDGF1, rs9378141/HLA-G, and rs3789612/PTPN22. The first four SNPs were in linkage disequilibrium with autoimmune-related diseases‒associated SNPs and were cis-expression quantitative trait loci in immune cells. The five SNPs-annotated genes were significantly enriched in immune processes. Higher polygenic risk scores and allele frequencies of rs3789612∗T, rs9378141∗C, and rs73075571∗G were significantly associated with autoimmune-related CSU phenotypes, including positive antithyroglobulin IgG, positive anti-FcεRIα IgG, total IgE <40 IU/ml, and positive antithyroid peroxidase IgG but not with atopic or allergic sensitized CSU phenotypes. This GWAS of CSU identifies five risk loci and reveals that CSU shares genetic overlap with autoimmune diseases and that genetic factors predisposing to CSU mainly manifest through associations with autoimmune traits.

Activation of aryl hydrocarbon receptor ameliorates rosacea-like eruptions in mice and suppresses the TLR signaling pathway in LL-37-induced HaCaT cells.

BACKGROUND: Toll-like receptor (TLR) 2, along with some chemokines, were found to be overexpressed in rosacea patients. Aryl hydrocarbon Receptor (AhR) activation inhibited the inflammatory responses triggered by TLR activation. The current study was conducted to evaluate the underlying mechanisms of AhR activation in rosacea models. MATERIALS AND METHODS: Seven-week-old female BALB/c mice received twice daily intradermal injections of LL-37 for 2 consecutive days. Thirty minutes after the second LL-37 injection, 1% or 0.5% AhR agonist benvitimod was administrated topically once per day for 3 consecutive days. HaCaT cells were treated with different concentrations of LL-37 and benvitimod, and were further infected with lentivirus to over-express TLR2. Expressions of TLR2, CCL5, CXCL9, CXCL10 and CXCL11 were evaluated using qRT-PCR, Western Blot or ELISA. RESULTS: AhR activation ameliorated LL-37-induced rosacea-like eruptions in mice by reductions in redness scores, redness areas and dermal inflammatory cell infiltrates. Elevated expressions of TLR2 and chemokines (CCL5, CXCL9, CXCL10 and CXCL11) following LL-37 treatment were decreased by AhR activation. In HaCaT cells receiving LL-37, TLR2 and the four chemokines were up-regulated, and levels of these chemokines were further enhanced after over-expressing TLR2. At 8 h after an administration of 10 µM benvitimod, gene expressions of TLR2 and the four chemokines in LL-37 treated HaCat cells were decreased, while their protein expressions were decreased for 24 h. CONCLUSION: AhR activation is beneficial in treating rosacea in a LL-37-induced rosacea mouse model and involves a suppression of the TLR signaling pathway in an HaCaT cell model of rosacea.

IgE and IgG Anti-Thyroid Autoantibodies in Chinese Patients With Chronic Spontaneous Urticaria and a Literature Review.

Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients (r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels (P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.

RTEL1 influences the abundance and localization of TERRA RNA.

Telomere repeat containing RNAs (TERRAs) are a family of long non-coding RNAs transcribed from the subtelomeric regions of eukaryotic chromosomes. TERRA transcripts can form R-loops at chromosome ends; however the importance of these structures or the regulation of TERRA expression and retention in telomeric R-loops remain unclear. Here, we show that the RTEL1 (Regulator of Telomere Length 1) helicase influences the abundance and localization of TERRA in human cells. Depletion of RTEL1 leads to increased levels of TERRA RNA while reducing TERRA-containing R loops at telomeres. In vitro, RTEL1 shows a strong preference for binding G-quadruplex structures which form in TERRA. This binding is mediated by the C-terminal region of RTEL1, and is independent of the RTEL1 helicase domain. RTEL1 binding to TERRA appears to be essential for cell viability, underscoring the importance of this function. Degradation of TERRA-containing R-loops by overexpression of RNAse H1 partially recapitulates the increased TERRA levels and telomeric instability associated with RTEL1 deficiency. Collectively, these data suggest that regulation of TERRA is a key function of the RTEL1 helicase, and that loss of that function may contribute to the disease phenotypes of patients with RTEL1 mutations.

Serum Detection of Anti-thyroid Peroxidase and Anti-thyroglobulin Antibodies in Chinese Patients With Pemphigus Vulgaris and Pemphigus Foliaceus and Literature Review.

Background: Pemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases. Purpose: To investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients. Methods: Antibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies. Results: 98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased presence of positive anti-TPO and anti-Tg antibodies and pemphigus, particularly for pemphigus vulgaris (PV). Such correlation was also observed in our own hospitalized PV patients, but not in pemphigus foliaceus (PF) patients. In addition, the status of anti-TPO and anti-Tg antibodies were also compared between females and males within PV patients, PF patients or controls, as well as compared for females or males between pemphigus patients and controls. In the analysis of T cell counts, we found abnormal low CD3 + T cell counts (< 690 n/µl) were only detected in patients whose thyroid antibody levels were less than 20 IU/ml. Conclusion: Pemphigus patients showed higher levels and antibody positivity of anti-TPO and anti-Tg antibodies than healthy controls. Further investigations are needed to identify the pathogenic functions of these antibodies in pemphigus, as well as to identify the potential shared susceptibility genes.

UVA influenced the SIRT1-miR-27a-5p-SMAD2-MMP1/COL1/BCL2 axis in human skin primary fibroblasts.

Both SIRT1 and UVA radiation are involved in cellular damage processes such as apoptosis, senescence and ageing. MicroRNAs (miRNAs) have been reported to be closely related to UV radiation, as well as to SIRT1. In this study, we investigated the connections among SIRT1, UVA and miRNA in human skin primary fibroblasts. Our results showed that UVA altered the protein level of SIRT1 in a time point-dependent manner. Using miRNA microarray, bioinformatics analysis, we found that knocking down SIRT1 could cause up-regulation of miR-27a-5p and the latter could down-regulate SMAD2, and these results were verified by qRT-PCR or Western blot. Furthermore, UVA radiation (5 J/cm2 ), knocking down SIRT1 or overexpression of miR-27a-5p led to increased expression of MMP1, and decreased expressions of COL1 and BCL2. We also found additive impacts on MMP1, COL1 and BCL2 under the combination of UVA radiation + Sirtinol (SIRT1 inhibitor), or UVA radiation + miR-27a-5p mimic. SIRT1 activator resveratrol could reverse damage changes caused by UVA radiation. Besides, absent of SIRT1 or overexpression of miR-27a-5p increased cell apoptosis and induced cell arrest in G2/M phase. Taken together, these results demonstrated that UVA could influence a novel SIRT1-miR-27a-5p-SMAD2-MMP1/COL1/BCL2 axis in skin primary fibroblasts, and may provide potential therapeutic targets for UVA-induced skin damage.

Shikonin inhibits CEBPD downregulation in IL­17­treated HaCaT cells and in an imiquimod­induced psoriasis model.

Psoriasis is a chronic inflammatory skin disease characterized by well­defined scaly papules and plaques. Interleukin (IL)­17 is involved in its pathogenesis and promotes the proliferation of epidermal keratinocytes through signal transducer and activator of transcription 3 (STAT3) activation. Shikonin, a natural naphthoquinone isolated from Lithospermum erythrorhizon, possesses anti­inflammatory and immunosuppressive properties and can suppress IL­17­induced vascular endothelial growth factor expression by inhibiting the JAK/STAT3 pathway. In the present study, MTS, iCELLigence and RT­qPCR were used to determine the optimal concentration and duration of IL­17 or shikonin acting on HaCaT cells. The changes in the expression levels of genes associated with the IL­6/STAT3 pathway in differentially treated cells were analyzed via RT2Profiler™ PCR Array. Small interfering RNA was used to silence the expression levels of the target gene CCAAT/enhancer­binding protein δ (CEBPD). Western blotting and immunohistochemistry were used to evaluate the effect of shikonin on imiquimod­induced psoriasis in mice and the expression levels of CEBPD. Shikonin reversed IL­17­mediated downregulation of the tumor suppressor CEBPD in HaCaT cells. Moreover, low levels of CEBPD in the imiquimod­induced mouse model of psoriasis were restored by shikonin treatment, which ameliorated excessive keratinocyte proliferation. Taken together, these findings suggest that CEBPD plays a key role in the pathogenesis of psoriasis and can be targeted by shikonin as a potential therapeutic strategy.

UVA Induced Oxidative Stress Was Inhibited by Paeoniflorin/Nrf2 Signaling or PLIN2.

Photodamages caused by UVA radiation induced oxidative injuries are closely related to photoaging and skin cancer. Paeoniflorin (PF), extracted from the root of Paeonia lactiflora, has been reported to be an effective antioxidant. PLIN2, known as adipose differentiation-related protein, has been previously involved in the regulation of oxidative stress. In this study, we were sought to investigate the photo-protective property of PF and PLIN2 in UVA-radiated human dermal fibroblasts (HDFs). HDFs were pre-treated with PF (800 µM) followed by UVA radiation (22.5 J/cm2). MTS activity, cell apoptosis, ROS, MDA, and SOD were detected, respectively. The expressions of Nrf2, HO-1, NQ-O1, and PLIN2 were determined using RT-qPCR or western blot. Nrf2 was silenced by siRNA, and PLIN2 was overexpressed via lentiviral transduction. Comparing to the UVA radiation, PF pre-treatment could prominently increase the MTS activity, decrease cell apoptosis, reduce the generations of ROS and MDA, increase the activity of SOD and increase the expression of Nrf2 and its target genes HO-1 and NQ-O1. When Nrf2 was knocked down, PF lost above protective properties. In addition, UVA induced oxidative stress led to upregulation of PLIN2 and the latter could be decreased by PF. Overexpression of PLIN2 improved MTS activity and reduced MDA level in HDFs. The combination of PLIN2 overexpression and PF pre-treatment corporately inhibited UVA-induced injury. Besides, we also found that PF and PLIN2 had a compensatory protection against UVA induced oxidative stress. In conclusion, our study demonstrated that UVA induced photodamages could be inhibited by PF via Nrf2/HO-1/NQ-O1 signaling pathway or by PLIN2, and the combination of PLIN2 overexpression and PF played additive effects against UVA-related oxidative stress.

Paeoniflorin Resists H2O2-Induced Oxidative Stress in Melanocytes by JNK/Nrf2/HO-1 Pathway.

Paeoniflorin (PF) possesses multiple biological functions including anti-oxidization. PF is the major bioactive ingredient of total glycosides of paeony (TGP), which could promote re-pigmentation of vitiligo. The study was sought to investigate the effects and potential signaling pathways of PF on hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes. The results showed that pretreatment with 50 µM PF significantly inhibited cell apoptosis, enhanced cell viability, and suppressed reactive oxygen species (ROS) accumulation by enhancing the productions of superoxide dismutase (SOD) and antioxidant enzymes catalase (CAT). Furthermore, PF activated c-Jun amino terminal kinase (JNK) and the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway to counteract H2O2-induced oxidative damage in PIG1 and PIG3V. Taken together, our study firstly demonstrates that PF resists H2O2-induced oxidative stress in melanocytes probably by activating JNK/Nrf2/HO-1 signaling, suggesting a potential therapeutic application of PF on vitiligo.

Anti-inflammatory effects of quercetin in a mouse model of MC903-induced atopic dermatitis.

In this study, the anti-inflammatory mechanisms of Quercetin (Que) on atopic dermatitis (AD)-like skin lesions was examined. The left ear of mice was applied with MC903, followed by Que. administration daily on the ear for 8 days. Then macroscopic and histologic examination was performed to detect the severity of skin lesions. In the skin section of AD mice, we observed that Que. could reduce the expression of CCL17, CCL22, IL-4, IL-6, IFN-γ and TNF-α. In vitro, the anti-inflammatory effects of Que. were examined on human keratinocytes (HaCaT cells) treated with IFN-γ/TNF-α. To unveil the lncRNAs' regulatory role on Que-activated anti-inflammatory function, the next-generation high-throughput sequencing was performed in HaCat cells with or without Que. treatment, which profiled the expression of lncRNAs and mRNAs, the results illustrated that lnc-C7orf30-2, a lncRNA expressed differentially, was correlated with IL-6 expression. Silencing of lnc-C7orf30-2 by RiboTM lncRNA Smart Silencer proved its role on IL-6 expression. Therefore, the results here demonstrated that topical administration of Que. plays a beneficial role in controlling AD symptoms, which may serve as potential candidate for AD treatment.

Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect.

Hyperthermia has been clinically utilized as an adjuvant therapy in the treatment of cervical carcinoma. However, thermotolerance induced by heme oxygenase-1 (HO-1), a stress-inducible cytoprotective protein, limits the efficacy of hyperthermic therapy, for which the exact mechanism remains unknown. In the present study, we found that heat treatment induced HO-1 expression and decreased copy number of HPV16 in cervical cancer cells and tissues from cervical cancer and precursor lesions. Knockdown of HO-1 stimulated autophagy accompanied by downregulation of X-linked inhibitor of apoptosis protein. Furthermore, silencing of HO-1 led to cell intolerance to hyperthermia, as manifested by inhibition of cell viability and induction of autophagic apoptosis. Moreover, HO-1 modulated hyperthermia-induced, autophagy-dependent antiviral effect. Thus, the findings indicate that blockade of HO-1 enhances hyperthermia-induced autophagy, an event resulting in apoptosis of cervical cancer cells through an antiviral mechanism. These observations imply the potential clinical utility of hyperthermia in combination with HO-1 inhibition in the treatment of cervical cancer.

The renin angiotensin system (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention.

Despite emergence of new systemic therapies, metastatic melanoma remains a challenging and often fatal form of skin cancer. The renin-angiotensin system (RAS) is a major physiological regulatory pathway controlling salt-water equilibrium, intravascular volume and blood pressure. Biological effects of the RAS are mediated by the vasoactive hormone angiotensin II (AngII) via two receptor subtypes, AT1R (encoded by AGTR1) and AT2R (encoded by AGTR2). We report decreasing expression and increasing CpG island methylation of AGTR1 in metastatic versus primary melanoma and detection in serum of methylated genomic DNA from the AGTR1 CpG island in metastatic melanoma implying that AGTR1 encodes a tumour suppressor function in melanoma. Consistent with this hypothesis, antagonism of AT1R using losartan or shRNA-mediated knockdown in melanoma cell lines expressing AGTR1 resulted in acquisition of the ability to proliferate in serum-free conditions. Conversely, ectopic expression of AGTR1 in cell lines lacking endogenous expression inhibits proliferation irrespective of the presence of AngII implying a ligand-independent suppressor function for AT1R. Treatment of melanoma cell lines expressing endogenous AT2R with either AngII or the AT2R-selective agonist Y6AII induces proliferation in serum-free conditions whereas the AT2R-specific antagonists PD123319 and EMA401 inhibit melanoma growth and angiogenesis and potentiate inhibitors of BRAF and MEK in cells with BRAF V600 mutations. Our results demonstrate that the RAS has both oncogenic and tumour suppressor functions in melanoma. Pharmacological inhibition of AT2R may provide therapeutic opportunities in melanomas expressing this receptor and AGTR1 CpG island methylation in serum may serve as a novel biomarker of metastatic melanoma.

Collagen Prolyl Hydroxylases Are Bifunctional Growth Regulators in Melanoma.

Appropriate post-translational processing of collagen requires prolyl hydroxylation, catalyzed by collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase, and is essential for normal cell function. Here we have investigated the expression, transcriptional regulation, and function of the collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase families in melanoma. We show that the collagen prolyl 3-hydroxylase family exemplified by Leprel1 and Leprel2 is subject to methylation-dependent transcriptional silencing in primary and metastatic melanoma consistent with a tumor suppressor function. In contrast, although there is transcriptional silencing of P4HA3 in a subset of melanomas, the collagen prolyl 4-hydroxylase family members P4HA1, P4HA2, and P4HA3 are often overexpressed in melanoma, expression being prognostic of worse clinical outcomes. Consistent with tumor suppressor function, ectopic expression of Leprel1 and Leprel2 inhibits melanoma proliferation, whereas P4HA2 and P4HA3 increase proliferation, and particularly invasiveness, of melanoma cells. Pharmacological inhibition with multiple selective collagen prolyl 4-hydroxylase inhibitors reduces proliferation and inhibits invasiveness of melanoma cells. Together, our data identify the collagen prolyl 3-hydroxylase and collagen prolyl 4-hydroxylase families as potentially important regulators of melanoma growth and invasiveness and suggest that selective inhibition of collagen prolyl 4-hydroxylase is an attractive strategy to reduce the invasive properties of melanoma cells.

Susceptibility of epithelial tumour cell lines to hyperthermia.

BACKGROUND: Human skin or mucosa exposes cells to both an internal and exogeneous thermal environment and the cells survive within a certain range of temperature. Exogeneous hyperthermia has been applied for the treatment of various types of cancers, fungal disease, and warts. OBJECTIVES: To determine whether different cellular components in the skin adapt to hyperthermic conditions differentially and further elucidate the mechanisms involved. MATERIALS & METHODS: Cell lines derived from normal and tumour epithelial cells were treated with hyperthermic conditions and tested for viability (using an MTS assay), apoptosis (using a FITC-conjugated annexin V apoptosis detection kit), and changes in intracellular calcium (using a calcium-sensitive fluorescent single-wavelength dye, Fluo-4 AM). RESULTS: Thermo-resistance of different cell types was different when cells were subjected to heat at 45̊C for 30 minutes. Stronger effects of hyperthermia were noted on cell viability and apoptosis in epidermal cells relative to their malignant counterparts, except for cell lines harbouring human papillomavirus (HPV). Hyperthermia had a much greater effect on cell viability and apoptosis in a HPV-negative cell line compared to HPV-positive cell lines. We further found that hyperthermia treatment resulted in a strong calcium influx which led to apoptotic cells. However, no obvious increase in apoptosis was observed in cells treated with the CRAC channel selective inhibitor, BTP2, before application of hyperthermia in all cell types, except three cervical cell lines harbouring HPV. CONCLUSION: We propose that hyperthermia results in a CRAC-related strong calcium influx which induces apoptosis, with the exception of HPV-positive cells.

MiR-155, a potential serum marker of extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD), a rare skin malignancy with non-specific manifestations, is often misdiagnosed as eczema of scrotum or tinea cruris. Although the diagnosis of EMPD could be confirmed by biopsy, it can be delayed as patients are reluctant to receive invasive operations. Herein, we investigated the serum miRNA expressions of EMPD patients and compared to that of the eczema of scrotum or tinea cruris patients as well as health volunteers for potential diagnostic markers for EMPD. METHODS: Altogether 45 subjects including 16 patients diagnosed with EMPD, 12 patients diagnosed with eczema of scrotum or tinea cruris and 17 healthy volunteers were enrolled in this study. Serum from all of subjects were collected to identify miRNAs (by miRNA array global normalization, RT-PCR validation, and receiver operating characteristic curve analysis) that could be potential diagnostic markers for EMPD. RESULTS: The miRNA array analyses revealed that the expressions of 37 miRNAs from the EMPD patients were different (change ≥4-fold) from health volunteers. Among these miRNAs, the expression of miR-155 was significantly increased (p < 0.01) in the EMPD patients as compared with that of the health volunteers and the eczema of scrotum or the tinea cruris patients (no difference between these two control groups). In addition, receiver operating characteristic (ROC) curve analysis showed that diagnostic capacities (defined as the area under curve of ROC) of miR-155 are 0.85 (as compared with health volunteers group) and 0.81 (as compared with the eczema of scrotum or the tinea cruris patients group), respectively. CONCLUSION: The serum miRNA expression of gene miR-155 in the EMPD patients was differentiated from that of other subjects warranting further validation of miR-155 as a diagnostic marker of EMPD.

G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner.

Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.