To Investigate the Diagnostic Accuracy and Prognostic Value of Amplitude-Integrated Electroencephalography (aEEG) in Neonatal Hypoxic Ischemic Encephalopathy.

Objective: The objective of this study is to investigate the diagnostic accuracy and prognostic value of amplitude-integrated electroencephalography (aEEG) in neonatal hypoxic ischemic encephalopathy (HIE). Methods: Fifty-three neonates with HIE admitted to our hospital from February 2020 to September 2021 were included in the encephalopathy group, while 22 healthy neonates born in our hospital during the same period were included in the healthy group. The neonates were separated into three subgroups based on their aEEG results: normal, slightly abnormal, and severely abnormal. We investigated the correlation between aEEG monitoring and HIE clinical grading, as well as the rate of HIE abnormal prognosis, and we analyzed the prognostic value of aEEG in HIE. Results: The aEEGs of all neonates in the healthy group were normal. In the encephalopathy group, there were 24 neonates with normal aEEGs (including 20 with mild HIE and 4 with moderate HIE), 16 neonates with mildly abnormal aEEGs (including 4 with mild HIE, 10 with moderate HIE, and 2 with severe HIE), and 13 neonates with severely abnormal aEEGs (including 4 with moderate HIE and 9 with severe HIE). A very close correlation between aEEG monitoring results and HIE grading and prognosis was found (P < .05). The head circumference of neonates with severely abnormal aEEGs was smaller than that of the other two groups and was significantly smaller than that of the healthy group (P < .05). However, there was no significant difference in the body length and weight of neonates in the severely abnormal aEEG group when compared to other groups (P > .05). Conclusion: The brain function of neonates with HIE can be accurately diagnosed with aEEG, and this diagnostic technique has a crucial application value in the early diagnosis and prognosis evaluation of neonatal HIE.

Analysis of risk factors for depression and anxiety related to the degree of asthma control in children according to gender.

OBJECTIVE: The purpose of the study was to investigate whether risk factors involved in the degree of asthma control were the same for children of both genders. METHODS: This cross-sectional study collected relevant data from 320 children with asthma attending the respiratory asthma clinic at a local children's hospital. All the patients passed the Asthma Control Test (ACT) or the Childhood Asthma Control Test (cACT), lung-function-related tests, the Children's Depression Inventory (CDI), the Screening Scale for Anxiety-Related Mood Disorders (SCARED), and the Family Personal Information Questionnaire. RESULTS: The study found that gender (p=0.034) was a risk factor for poor asthma control and that girls (odds ratio [OR]=1.669, p=0.042) were more likely to have poor asthma control than boys. Univariate logistic regression analysis found that severe wasting (OR=0.075, p=0.021), depression (OR=43. 550, p<0.001), anxiety (OR=4.769, p=0.036), FEV1% (OR=0.970, p=0.043), FEV1/FVC% (OR=0.921, p=0. 008), and PEF% (OR=0.961, p=0.012) were risk factors for poor asthma control in girls. CONCLUSION: The risk factors for the degree of asthma control in children with asthma appeared to vary according to gender.

Specific Targeting of STAT3 in B Cells Suppresses Progression of B Cell Lymphoma.

The signal transducer and activator of transcription 3 (STAT3), which regulates multiple oncogenic processes, has been found to be constitutively activated in lymphoma, suggesting its potential as a therapeutic target. Here, we constructed an anti-CD19-N-(4-carboxycyclohexylmethyl) maleimide N-hydroxysuccinimide ester (SMCC)-protamine (CSP)-STAT3 small interfering RNA (siRNA) conjugate and demonstrated that the CSP-STAT3 siRNA conjugate could specifically bind to normal B cells and A20 lymphoma cells in vitro. It decreased the STAT3 expression in B cell lymphoma cell lines (A20, SU-DHL-2 and OCI-Ly3), resulting in reduced proliferation of lymphoma cells featured with lower S-phase and higher apoptosis. Using an A20 transplantable lymphoma model, we found that the CSP-STAT3 siRNA conjugate significantly inhibited tumor growth and weight. Ki-67, p-STAT3, STAT3, and serum IL-6 levels were all significantly reduced in A20-bearing mice treated with CSP-STAT3 siRNA. These findings indicate that specifically targeting STAT3 siRNA to B cell lymphoma cell lines can significantly decrease STAT3 activity and inhibit tumor progression in vitro and in vivo, suggesting its potential utilization for cancer treatment.

Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk.

Lung cancer is one of the malignant tumors, and genetic background is a risk factor in lung cancer that cannot be neglected. In this study, we aimed to find out the effect of MRPS30-DT and NINJ2 variants on lung cancer risk. In this study, the seven selected single-nucleotide polymorphisms (SNPs) of MRPS30-DT and NINJ2 were genotyped in 509 lung cancer patients and 501 healthy controls based on the Agena MassARRAY platform. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis to evaluate association between gene polymorphisms and lung cancer risk. False-positive report probability was also used to assess false-positive results. Furthermore, the interaction between SNPs was analyzed by multifactor dimensionality reduction to predict lung cancer risk. We identified the genotype TA of rs16901963 (T < A) in MRPS30-DT as a protective factor against lung cancer, while rs16901963-TT was significantly associated with an increased risk of lung cancer. We also revealed that the effect of MRPS30-DT and NINJ2 variants on the risk of lung cancer was dependent on age, gender, smoking, and drinking status. In conclusion, this study first proved that MRPS30-DT and NINJ2 variants played important roles in affecting the susceptibility to lung cancer.

Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis.

Metastasis is the leading cause of cancer-related deaths and myeloid cells are critical in the metastatic microenvironment. Here, we explore the implications of reprogramming pre-metastatic niche myeloid cells by inducing trained immunity with whole beta-glucan particle (WGP). WGP-trained macrophages had increased responsiveness not only to lipopolysaccharide but also to tumor-derived factors. WGP in vivo treatment led to a trained immunity phenotype in lung interstitial macrophages, resulting in inhibition of tumor metastasis and survival prolongation in multiple mouse models of metastasis. WGP-induced trained immunity is mediated by the metabolite sphingosine-1-phosphate. Adoptive transfer of WGP-trained bone marrow-derived macrophages reduced tumor lung metastasis. Blockade of sphingosine-1-phosphate synthesis and mitochondrial fission abrogated WGP-induced trained immunity and its inhibition of lung metastases. WGP also induced trained immunity in human monocytes, resulting in antitumor activity. Our study identifies the metabolic sphingolipid-mitochondrial fission pathway for WGP-induced trained immunity and control over metastasis.

Axillary fossaa microbial dysbiosis and its relationship with axillary osmidrosis patients.

BACKGROUND: Skin is one of the largest human bacterial reservoirs, especially the human axilla. The microbiota of the human axilla plays an important role in the creation of axillary smell. AIMS: To explore the structure and composition of the axillary fossa microbiota between bromhidrosis patients and normal people, skin samples were collected from the armpits of 40 individuals, including 20 patients (10 males (aM), 10 females (aF), osmidrosis), and 20 healthy individuals (10 males (NM), 10 females (NF), control). METHODS: High-throughput sequencing of the 16S rRNA gene was carried out on a Hiseq2500 platform with the V3+V4 regions. RESULTS: According to the bacterial Shannon diversity index and Simpson, we found that aF was significantly higher than the control but aM had no obvious distinction. Actinobacteria, Firmicutes, Proteobacteria and Deinococcus-Thermus were the dominant phyla in the four groups. Actinobacteria was distinctly higher in aM, while Firmicutes was significantly lower in aM. Furthermore, the aF displayed inverse results with aM. Corynebacterium-1 and Staphylococcus were the dominant genera in the four groups. Interestingly, Staphylococcus was the most abundant in aF, and Corynebacterium-1 was the dominant genus in aM and Corynebacterium-kroppenstedtii was significantly different in aM. Moreover, functional capacity analysis showed that genes associated with amino acid metabolism and lipid metabolism were higher in aM than in other groups, while pyruvate metabolism (carbohydrate metabolism) was obviously high in aF. CONCLUSION: There were clearly distinct of axillary microbiota undergoes changes between bromhidrosis patients and controls. Staphylococcus and Corynebacterium-1 in aF and aM, respectively, were detected with distinctly elevated proportions, which might be strongly related to human axilla odor.

Neutrophil-Derived Semaphorin 4D Induces Inflammatory Cytokine Production of Endothelial Cells via Different Plexin Receptors in Kawasaki Disease.

Inflammation of endothelial cells (ECs) plays an important role in the pathogenesis of coronary artery lesions (CALs) in Kawasaki disease (KD). Semaphorin 4D (Sema4D) is the first semaphorin shown to have immunoregulatory functions by interacting with its receptors-plexin Bs. Recently, Sema4D has been reported to exert a proinflammatory effect on the endothelium and to be involved in cardiovascular disease. However, the role of Sema4D in KD remains unknown. This study was aimed at revealing the change of soluble Sema4D (sSema4D) in the serum of patients with KD and the effect of the sSema4D-plexin axis on the production of proinflammatory cytokines from human coronary endothelial cells (HCAECs) stimulated with sera from KD patients. Our results showed that serum sSema4D levels were specifically elevated in KD patients, especially in those with CALs, and correlated positively with disease severity and serum concentrations of interleukin- (IL-) 1ß, IL-6, and IL-8. The disintegrin and metalloproteinase domain 17- (AMAM17-) mediated Sema4D shedding from neutrophils contributed to the elevation of sSema4D in the serum of KD patients. Furthermore, we found that Sema4D induced IL-1ß production of HCAECs via plexin B2, whereas it promoted IL-6 and IL-8 production via plexin B1. Moreover, the expression of both plexin B1 and plexin B2 was upregulated in HCAECs treated with KD sera, and silencing of the two plexin receptors suppressed the overexpression of IL-1ß, IL-6, and IL-8 in KD serum-treated HCAECs. Thus, our findings indicated that sSema4D released from neutrophils participates in the pathogenesis of KD-CALs by promoting inflammatory cytokine production of ECs via both plexin B1 and plexin B2, and Sema4D may be a novel predictor for KD-CALs and a candidate therapeutic target for anti-inflammatory strategies of KD.

Silencing KPNA2 inhibits IL-6-induced breast cancer exacerbation by blocking NF-κB signaling and c-Myc nuclear translocation in vitro.

AIMS: Recently, studies indicated that inflammation could exacerbate the development of BC. Karyopherin α-2 (KPNA2) is a molecule which modulates nucleocytoplasmic transport and is involved in malignant cellular behavior and carcinogenesis. Our study aims to elucidate the role of KPNA2 in BC pathogenesis and explore the mechanism of KPNA2 in regulating inflammation-induced BC exacerbations. MAIN METHODS: We measured the expression of KPNA2 in BC cells. Through loss-of-function experiments, the functional role of KPNA2 in MCF-7 and MDA-MB-468 cells was evaluated. SK-BR-3 cells were treated with IL-6 as an inflammatory in vitro model of BC. ELISA determination exhibited the contents of cytokines. RANKL and leptomycin B treatments activated NF-κB signaling and inhibited the nuclear translocation of c-Myc, respectively. KEY FINDINGS: The results showed that KPNA2 was significantly up-regulated in BC and silencing KPNA2 inhibited the proliferation, migration and invasion of BC cells, while the cycle arrest was induced, via blocking NF-κB signaling and c-Myc nuclear translocation. IL-6 stimulated the secretions of IL-8 and IL-17 in BC cells, and elevated KPNA2 expression. However, KPNA2 knockdown suppressed the inflammatory responses and malignant progression of BC induced by IL-6. SIGNIFICANCE: In conclusion, our study illustrated that KPNA2 regulated BC development, as well as IL-6-induced inflammation and exacerbation, via NF-κB signaling and c-Myc nuclear translocation. This may provide a novel target for BC therapy.

Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer.

Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving the protumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer. c-Maf controls many M2-related genes and has direct binding sites within a conserved noncoding sequence of the Csf-1r gene and promotes M2-like macrophage-mediated T cell suppression and tumor progression. c-Maf also serves as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis, thus promoting M2-like macrophage polarization and activation. Additionally, c-Maf is highly expressed in tumor-associated macrophages (TAMs) and regulates TAM immunosuppressive function. Deletion of c-Maf specifically in myeloid cells results in reduced tumor burden with enhanced antitumor T cell immunity. Inhibition of c-Maf partly overcomes resistance to anti-PD-1 therapy in a subcutaneous LLC tumor model. Similarly, c-Maf is expressed in human M2 and tumor-infiltrating macrophages/monocytes as well as circulating monocytes of human non-small cell lung carcinoma (NSCLC) patients and critically regulates their immunosuppressive activity. The natural compound ß-glucan downregulates c-Maf expression on macrophages, leading to enhanced antitumor immunity in mice. These findings establish a paradigm for immunosuppressive macrophage polarization and transcriptional regulation by c-Maf and suggest that c-Maf is a potential target for effective tumor immunotherapy.

ΗΙF1α, EGR1 and SP1 co-regulate the erythropoietin receptor expression under hypoxia: an essential role in the growth of non-small cell lung cancer cells.

BACKGROUND: Overexpression of erythropoietin (EPO) and EPO receptor (EPO-R) is associated with poor prognosis in non-small-cell lung carcinoma (NSCLC). Hypoxia, a potent EPO inducer, is a major stimulating factor in the growth of solid tumors. However, how EPO-R expression is regulated under hypoxia is largely unknown. METHODS: The role of EPO-R in NSCLC cell proliferation was assessed by RNA interference in vitro. Luciferase reporter assays were performed to map the promoter elements involved in the EPO-R mRNA transcription. Nuclear co-immunoprecipitation and chromatin immunoprecipitation were performed to assess the interaction among transcription factors HIF1α, SP1, and EGR1 in the regulation of EPO-R under hypoxia. The expression of key EPO-R transcription factors in clinical specimens were determined by immunohistochemistry. RESULTS: Hypoxia induced a dosage and time dependent EPO-R mRNA expression in NSCLC cells. Knockdown of EPO-R reduced NSCLC cell growth under hypoxia (P < 0.05). Mechanistically, a SP1-EGR1 overlapped DNA binding sequence was essential to the hypoxia induced EPO-R transcription. In the early phase of hypoxia, HIF1α interacted with EGR1 that negatively regulated EPO-R. With the exit of EGR1 in late phase, HIF1α positively regulated EPO-R expression through additive interaction with SP1. In clinical NSCLC specimen, SP1 was positively while EGR1 was negatively associated with active EPO-R expression (P < 0.05). CONCLUSIONS: HIF1α, SP1 and EGR1 mediated EPO-R expression played an essential role in hypoxia-induced NSCLC cell proliferation. Our study presents a novel mechanism of EPO-R regulation in the tumor cells, which may provide information support for NSCLC diagnosis and treatment.

Local blockage of self-sustainable erythropoietin signaling suppresses tumor progression in non-small cell lung cancer.

Functional significance of co-expressed erythropoietin (EPO) and its receptor (EPOR) in non-small cell lung cancer (NSCLC) had been under debate. In this study, co-overexpression of EPO/EPOR was confirmed to be positively associated with poor survival in NSCLC. The serum EPO in 14 of 35 enrolled NSCLC patients were found elevated significantly and decreased to normal level after tumor resection. With primary tumor cell culture and patient-derived tumor xenograft (PDX) mouse model, the EPO secretion from the tumors of these 14 patients was verified. Then, we proved the patient derived serum EPO was functionally active and had growth promotion effect in EPO/EPOR overexpressed but not in EPO/EPOR under-expressed NSCLC cells. We also illustrated EPO promoted NSCLC cell proliferation through an EPOR/Jak2/Stat5a/cyclinD1 pathway. In xenograft mouse model, we proved local application of EPO neutralizing antibody and short hairpin RNA (shRNA) against EPOR effectively inhibited the growth of EPO/EPOR overexpressed NSCLC cells and prolonged survivals of the mice. Finally, EPO/EPOR/Jak2/Stat5a/cyclinD1 signaling was found to be a mediator of hypoxia induced growth in EPO/EPOR overexpressed NSCLC. Our results illustrated a subgroup of NSCLC adapt to hypoxia through self-sustainable EPO/EPOR signaling and suggest local blockage of EPO/EPOR as potential therapeutic method in this distinct NSCLC population.

IL-1ß upregulates Muc5ac expression via NF-κB-induced HIF-1α in asthma.

The manifest and important feature in respiratory diseases, including asthma and COPD (chronic obstructive pulmonary disease), is the increased numbers and hypersecretion of goblet cells and overexpression of mucins, especially Muc5ac. Many proinflammatory cytokines play important roles in goblet cell metaplasia and overproduction of Muc5ac. However, the effect of IL-1ß on Muc5ac expression in asthma remains unknown. Here, we detected the correlation between IL-1ß and Muc5ac in asthma patients and further explored the mechanism of IL-1ß-induced Muc5ac overexpression. Our results showed that Muc5ac and IL-1ß were up-regulated in 41 patients with asthma and that Muc5ac overexpression was related with IL-1ß in asthma (R2=0.668, p≪0.001). Furthermore, the correlation between IL-1ß and Muc5ac is higher in severe group than that in moderate group. In vitro experiments with normal human bronchial epithelial cells (NHBECs) showed that IL-1ß up-regulated Muc5ac expression in NHBEC in a time- and dosage-dependent manner. Hypoxia-induced HIF-1α was responsible for Muc5ac expression mediated by IL-1ß. Knocking down HIF-1α by siRNA decreased Muc5ac expression under hypoxia even in IL-1ß-treated NHBEC cells. Luciferase reporter assay showed that HIF-1α enhanced Muc5ac promoter activity in HEK293T cells. HIF-1α could specifically bind to the promoter of Muc5ac by EMSA. The correlation among IL-1ß, HIF-1α and Muc5ac was observed in patients with asthma. Mechanically, NF-κB activation was essential to IL-1ß-induced HIF-1α upregulation via the canonical pathway of NF-κB. The level of nuclear p65, a subunit of NF-κB, was obviously increased in NHBEC cells under IL-1ß treatment. IL-1ß did not change either HIF-1α or Muc5ac expression when inhibiting NF-κB signaling with Bay11-7082, an inhibitor of NF-κB. Collectively, we concluded that IL-1ß up-regulated Muc5ac expression via NF-κB-induced HIF-1α in asthma and provided a potential therapeutic target for asthma.

Changes in 11ß-Hydroxysteroid Dehydrogenase and Glucocorticoid Receptor Expression in Kawasaki Disease.

BACKGROUND AND OBJECTIVES: This study aims to investigate the significance of changes in the expression 11ß-hydroxysteroid dehydrogenase (11ß-HSD) and glucocorticoid receptor (GR) for the development of Kawasaki disease (KD). SUBJECTS AND METHODS: Real-time polymerase chain reaction was performed to determine the mRNA expression levels of GR and 11ß-HSD in peripheral blood monocytes, both in the acute phase of the disease and after treatment. Western blotting was performed to determine the protein expression levels of GR and 11ß-HSD. RESULTS: The expression levels of GRß, GRß, and 11ß-HSD1 mRNA in the acute phase were significantly higher than levels at baseline (p<0.01) and after treatment (p<0.05). The 11ß-HSD2 mRNA levels were lower in the acute phase than in the normal group (p<0.01), and they were significantly higher after treatment than before (p<0.01). Western blot results were consistent with the real-time PCR results. The coronary artery lesion group exhibited significantly different 11ß-HSD2 expression levels from that of the group with normal coronary arteries (p<0.01). CONCLUSION: GR and 11ß-HSD expression changes in the acute phase of KD are important factors for regulating inflammatory responses in KD.

Lectin PCL inhibits the Warburg effect of PC3 cells by combining with EGFR and inhibiting HK2.

Prostatic carcinoma is the most aggressive tumor in adult men. Warburg effect is an important characteristic of tumor cell metabolism including prostate cancer cells, in which hexokinase 2 (HK2), a major rate-limiting enzyme involved in Warburg effect, is selectively upregulated. The lectin PCL is a mannose binding lectin which induces tumor cell apoptosis and autophagy. In the present study, we report that PCL could lower glucose consumption and lactate production, shift the Warburg effect by inhibiting the expression of HK2 in PC3 cells and the suppression of HK2 by siRNA reversed the effect of PCL on glucose consumption and lactate production. The expression of HK2 is closely related to epidermal growth factor receptor (EGFR) and downstream signaling pathway activation, therefore, we investigated the interaction of PCL with EGFR by western blot analysis and found that PCL could suppress the binding of epidermal growth factor (EGF) with EGFR and HK2 expression. Also, we explored the binding mechanism between the PCL and EGFR through molecular docking and molecular dynamics simulations and found that PCL bocked the active site of EGFR which is also the binding site of the nature ligand EGF, the resulting conformation has higher stability than EGF in complex with EGFR. The results indicated that PCL could competitively bind to EGFR binding pocket and then prevent EGF from binding to EGFR, blocking the autophosphorylation of the EGFR tyrosine kinase, after that the EGFR activation is inhibited. Collectively, our studies concluded that PCL inhibits tumor cell glycolysis by combining with EGFR and reducing HK2 expression.

Gene expression profiling of microRNAs associated with UCA1 in bladder cancer cells.

Emerging evidence indicates that non-coding RNAs, such as lncRNAs and microRNAs, play important roles in diverse diseases, such as cancer, immune diseases and cardiovascular diseases. Interestingly, lncRNAs could directly or indirectly regulate the expression of miRNAs. However, the expression profiling of miRNAs associated with UCA1 in bladder cancer remains unknown. Here, we used Illumina deep sequencing to sequence miRNA libraries from both the UCA1 knockdown and normal high-expression 5637 cells. We identified 225 and 235 miRNAs expressed in 5637 cells of normal high-expression and knockdown of UCA1, respectively. Overall, expression of 75 miRNAs showed significant difference associated with UCA1, of which 38 were upregulated and 37 downregulated with UCA1 knockdown. GO analysis of the host target genes revealed that these aberrantly regulated miRNAs were involved in complex cellular pathways, including biological process, cellular component and molecular function. We selected 8 candidate miRNAs associated with UCA1 and predicted their targeted mRNAs, and found that p27kip1 was a crucial downstream molecule for these 8 miRNAs, especially for miR-196a. KEGG pathway analysis showed that PI3K-Akt signaling pathway was involved in regulating these 8 candidant miRNAs. Among these 8 candidant miRNAs, we observed the correlation among UCA1, miR-196a and the host target mRNA, p27kip1, in bladder cancer cells and tissues. UCA1 was upregulated by miR-196a and positively correlated with miR-196a, whereas UCA1 and miR-196a were negatively correlated with p27kip1, which was downregulated in bladder cancer patients. Thus, our findings provided valuable information on miRNAs associated with UCA1 in bladder cancer, which could be helpful to further explore the related genes and molecular networks fundamental in bladder cancer progression.

[Up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) of CD4⁺ T cells is positively related to RORC and IL-17A in patients with Kawasaki disease].

OBJECTIVE: To investigate the expression of serum- and glucocorticoid-inducible kinase 1 (SGK1) in Kawasaki disease (KD) and explore the correlations between SGK1 and Th17 cell-related cytokines [retinoic-acid-related orphan nuclear receptor C (RORC), interleukin 17A (IL-17A), IL-6] in KD. METHODS: Thirty patients with KD [(2.8 ± 1.4) years old], 30 healthy volunteers [(2.6 ± 1.6) years old] and 25 patients with infectious disease (ID) [(2.2 ± 1.5) years old] were recruited. The percentage of Th17 cells in CD4⁺ T cells was analyzed using flow cytometry. The mRNA levels of RORC and SGK1 in CD4⁺ T cells were detected using real-time quantitative PCR. The serum levels of IL-17A and IL-6 were analyzed by ELISA. RESULTS: Compared with healthy volunteers and patients with ID, the percentage of Th17 cells in CD4⁺ T cells significantly increased in KD [(3.57 ± 0.62)% vs (0.51 ± 0.07)% or (1.72 ± 0.36)%]. The serum levels of IL-17A and IL-6 in KD were much higher than those in healthy volunteers and patients with ID. The mRNA levels of RORC and SGK1 in KD were remarkably elevated compared with healthy volunteers and patients with ID. The level of SGK1 in coronary artery lesion (CAL) group of KD was significantly higher than that in KD patients with normal coronary artery (CAN). SGK1 was reduced in KD after intravenous immunoglobulin (IVIG) treatment. What's more, the decrease of SGK1 was more obviously in the CAL group than in the CAN group. In addition, SGK1 expression in KD was positively correlated with RORC and IL-17A, but not with IL-6. CONCLUSION: SGK1 was up-regulated in CD4⁺ T cells and was positively correlated with RORC and IL-17A in the patients with KD.

FOXP3 suppresses breast cancer metastasis through downregulation of CD44.

Forkhead box protein 3 (FOXP3) plays an important role in breast cancer as an X-linked tumor suppressor gene. However, the biological functions and significance of FOXP3 in breast cancer metastasis remain unclear. Here, we find that, clinically, nuclear FOXP3 expression is inversely correlated with breast cancer metastasis. Moreover, we demonstrate that FOXP3 significantly inhibits adhesion, invasion and metastasis of breast cancer cells in vivo and in vitro. In addition, the adhesion molecule CD44 is found to be suppressed by FOXP3 through transcriptome sequence analysis (RNA-seq). A luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay identify CD44 as a direct target of FOXP3. The expression of CD44 is downregulated by FOXP3 in breast cancer cells. Importantly, anti-CD44 antibody reverses the FOXP3 siRNA-induced effects on the breast cancer cells in vitro and FOXP3 expression level in the nucleus of breast cancer cells is inversely correlated with CD44 expression level in clinic breast cancer tissues. Taken together, the results from the present study suggest that FOXP3 is a suppressor of breast cancer metastasis. FOXP3 directly binds to the promoter of CD44 and inhibits its protein expression, thereby suppressing adhesion and invasion of human breast cancer cells. This finding highlights the therapeutic potential of FOXP3-CD44 signaling to inhibit breast cancer metastasis.

Microarray expression profile of lncRNAs and the upregulated ASLNC04080 lncRNA in human endometrial carcinoma.

Long non-coding RNAs (lncRNAs) have been recognized as a regulator of gene expression, and the deregulation of lncRNAs have been reported to be correlated with carcinogenesis and cancer progression. To explore the function of lncRNA in endometrial carcinoma, we analyzed the expression profiles of lncRNAs and coding genes in 3 paired endometrial carcinoma and adjacent non-tumor tissues, using a microarray. The results of microarray analysis indicated a significant difference in lncRNA and coding gene expression between endometrial carcinoma and their paired adjacent non-tumor tissues. A total of 53 lncRNAs (fold change >2.0, p-value <0.05) were found to be differently expressed in endometrial carcinoma compared to the normal controls. Among these ASLNC04080 was the most significantly upregulated lncRNA in microarray data, highly expressed in 22 out of 24 endometrial carcinoma tissues and HEC-1-B cell line. ASLNC04080 is 1867nt in length, consist of 6 exons, and locates at 1 p35.3(chr1: -28905061 - -28909492). In addition, 46 coding gene transcripts were differentially expressed (fold change >2.0, p-value <0.05) between endometrial carcinoma and adjacent non-tumor tissues. Pathway and gene ontology analysis demonstrated that these deregulated transcripts were involved in multiple signal pathways, biological processes, cellular components and molecular functions. Moreover, the ASLNC04080 lncRNA expression was correlated with 19 coding genes, and may contribute to endometrial carcinoma genesis and progression by co-regulating with coding gene. Expression inhibition of lncRNA ASLNC04080 in HEC-1-B cells caused repression of cell proliferation, increased cell apoptosis, and G1 phase arrest. These results suggested a potential function of ASLNC04080 in endometrial carcinoma genesis and progression.

Long non-coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the mTOR-STAT3/microRNA143 pathway.

Cancer cells preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. Emerging evidence has shown that long non-coding RNAs (lncRNAs) act as key regulators of multiple cancers. However, it remains largely unexplored whether and how lncRNA regulates glucose metabolism in cancer cells. In this study, we show that lncRNA UCA1 promotes glycolysis in bladder cancer cells, and that UCA1-induced hexokinase 2 (HK2) functions as an important mediator in this process. We further show that UCA1 activates mTOR to regulate HK2 through both activation of STAT3 and repression of microRNA143. Taken together, these findings provide the first evidence that UCA1 plays a positive role in cancer cell glucose metabolism through the cascade of mTOR-STAT3/microRNA143-HK2, and reveal a novel link between lncRNA and the altered glucose metabolism in cancer cells.

Upregulation of long non-coding RNA urothelial carcinoma associated 1 by CCAAT/enhancer binding protein α contributes to bladder cancer cell growth and reduced apoptosis.

Long non-coding RNA urothelial carcinoma associated 1 (lncRNA-UCA1) is upregulated in bladder cancer and plays a pivotal role in bladder cancer progression and metastasis. Recent studies and our research found that lncRNA-UCA1 may be an important biomarker and therapeutic target for bladder cancer. However, the molecular mechanism involved in the upregulation of lncRNA-UCA1 in bladder cancer is largely unknown. In the present study, we showed that lncRNA-UCA1 expression in bladder cancer cells was upregulated by transcription factor CCAAT/enhancer binding protein α (C/EBPα), which was the only candidate transcription factor simultaneously predicted by a total of five bioinformatical software programs. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay indicated that C/EBPα bound to the lncRNA-UCA1 core promoter region in vitro and in vivo. The luciferase assays further showed that there was a point mutation (A231G) in the C/EBPα binding site of the lncRNA-UCA1 core promoter in various bladder cancer cell lines, which in turn significantly increased the transcriptional activity of lncRNA-UCA1. We also demonstrated that C/EBPα siRNA treatment contributed to the downregulation of lncRNA-UCA1 expression, whereas overexpression of C/EBPα enhanced lncRNA-UCA1 expression. Furthermore, lncRNA-UCA1 transcriptional repression by C/EBPα siRNA sharply reduced cell viability and induced cell apoptosis in vitro. Collectively, our results provide a novel therapeutic strategy for bladder cancer by effectively interrupting the binding of the lncRNA-UCA1 promoter and certain transcription factors, so as to reverse the upregulation of lncRNA-UCA1 and prevent bladder cancer progression.