HNRNPA2B1 induces cell proliferation and acts as biomarker in breast cancer.

BACKGROUND: Numerous studies have shown that m6A plays an important regulatory role in the development of tumors. HNRNPA2B1, one of the m6A RNA methylation reading proteins, has been proven to be elevated in human cancers. OBJECTIVE: In this study, we aimed to identify the role of HNRNPA2B1 in breast cancer. METHODS: HNRNPA2B1 expression was investigated via RT-qPCR and TCGA database in breast cancer. Then, the function of HNRNPA2B1 on cancer cell was measured by CCK8 assays, colony formation and scratch assays. In addition, HNRNPA2B1 expression in BRCA was explored via the Wilcoxon signed-rank test, KruskalWallis test and logistic regression. The association with HNRNPA2B1 expression and survival were considered by KaplanMeier and Cox regression analyses. The biological function of HNRNPA2B1 was analyzed via gene set enrichment analysis (GSEA) and the cluster Profiler R software package. RESULTS: We found that HNRNPA2B1 was highly expressed and induced cell proliferation and migration in breast cancer. Moreover, we observed HNRNPA2B1 induced tumor growth in vivo. In addition, we also found HNRNPA2B1 expression was associated with characteristics and prognosis in breast cancer patients. CONCLUSION: Our findings suggested that HNRNPA2B1 promoted tumor growth and could function as a new potential molecular marker in breast cancer.

Hp0521 inhibited the virulence of H. pylori 26,695 strain via regulating CagA expression.

Hp0521 is the number of cag pathogenicity island (cagPAI) family in Helicobacter pylori (H. pylori, Hp), which encoded Cag2 protein. The aim of this study was to investigate the role of hp0521 on the H. pylori 26,695 strain. We constructed the recombinant prokaryotic expression plasmid pET-32a-hp0521 and pET-32a-hpc0521. Then, we co-cultured the H. pylori wild strain 26,695 and Δhp0521 strain with GES-1 cells to detect CagA protein transport and IL-8 secretion. We found that Δhp0521 mutation increased the expression of cagA, rpoB and promoted the transportation of CagA protein in GES-1 cells. In addition, we also observed that Δhp0521 mutation had no effect on other cagPAI protein stability and the expression of IL-8. Our findings suggested that hp0521 may down-regulated the expression of cagA, rpoB and inhibited the transportation of CagA protein in GES-1 cells and had no effect on growth.

Runx1 Deficiency Promotes M2 Macrophage Polarization Through Enhancing STAT6 Phosphorylation.

Our previous study had demonstrated that Runx1 promoted LPS-induced macrophage inflammatory response, however, the role of Runx1 in M2 macrophage polarization still remains largely unknown. This study was conducted to investigate the role of Runx1 in IL-4/IL-13-induced M2 macrophage polarization and its potential regulatory mechanism. We found that exposure of macrophages to IL-4/IL-13 induced a remarkable increasement in Runx1 expression level. Specifically, we established genetically modified mice lacking Runx1 in myeloid cells, including macrophages. RNA-Seq was performed to identify differentially expressed genes (DEGs) between Runx1 knockout and WT control bone marrow-derived macrophages (BMDMs). We identified 686 DEGs, including many genes which were highly expressed in M2 macrophage. In addition, bioinformatics analysis indicated that these DEGs were significantly enriched in extracellular matrix-related processes. Moreover, RT-qPCR analysis showed that there was an obvious upregulation in the relative expression levels of M2 marker genes, including Arg1, Ym1, Fizz1, CD71, Mmp9, and Tgm2, in Runx1 knockout macrophages, as compared to WT controls. Consistently, similar results were obtained in the protein and enzymatic activity levels of Arg1. Finally, we found that the STAT6 phosphorylation level was significantly enhanced in Runx1 knockout macrophages, and the STAT6 inhibitor AS1517499 partly reduced the upregulated effect of Runx1 deficiency on the M2 macrophage polarization. Taken together, Runx1 deficiency facilitates IL-4/IL-13-induced M2 macrophage polarization through enhancing STAT6 phosphorylation.

The role of exosomal lncRNAs in cancer biology and clinical management.

Exosomes play a vital role in cell-cell communication within the cancer microenvironment. Exosomal long noncoding RNAs (lncRNAs) are important regulators in cancer development and are involved in multiple processes, including cancer cell proliferation, angiogenesis, metastasis, drug resistance, and immunomodulation. Changes in the levels of exosomal lncRNAs often appear with the occurrence and development of cancer. Therefore, exosomal lncRNAs can be used as biomarkers for cancer diagnosis and prognosis. Exosomal lncRNAs can also indicate the treatment response of patients receiving chemotherapy. Moreover, exosomal lncRNAs are potential therapeutic targets for cancer treatment. In this review, we summarize the role of exosomal lncRNAs in cancer biology as well as in clinical management. A more comprehensive and in-depth understanding of the role of exosomal lncRNAs in cancer may help us better understand the mechanism of cancer development and clinically manage cancer patients.

Butyrate functions in concert with myeloid-derived suppressor cells recruited by CCR9 to alleviate DSS-induced murine colitis.

Ulcerative colitis (UC) is a precancerous disease caused mainly by a combination of genetic susceptibility, environmental factors and microbiota dysbiosis. As a kind of short-chain fatty acid (SCFA), butyrate has been shown to be closely related to the progression of colitis. However, the exact regulatory mechanism of butyrate in colitis needs to be further elucidated. In our current research, the effects of butyrate were examined in a dextran sulfate sodium (DSS)-induced murine colitis model, which simulates human UC. The administration of butyrate significantly reversed the signs of colitis and alleviated colonic histological damage in DSS­induced colitis. The transcription levels of the main proinflammatory mediators, including tumor necrosis factor-α, interleukin-6 and interleukin-12, were also reduced, as determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). This indicates that butyrate could alleviate DSS-induced colitis by inhibiting proinflammatory mediators. In addition, we found that myeloid-derived suppressor cells (MDSCs), which have an inflammation-relieving effect, did not effectively alleviate DSS­induced colitis but showed a compensatory increase in the DSS group. However, the compensatory increase in MDSCs in the DSS group significantly decreased after butyrate treatment. Moreover, the chemokine receptor CCR9, which mediates the homing of intestinal immune cells, also showed consistent changes similar to MDSCs. Butyrate alone did not have the aforementioned effects on mice. Thus, butyrate may effectively relieve DSS­induced colitis by synergistic regulatory effects with MDSCs, which migrate and gather through CCR9 recruitment.

Vitamin D Deficiency May Not Be an Independent Risk Factor for Peripheral Arterial Disease in Middle-Aged and Elderly Patients with Type 2 Diabetes in China.

BACKGROUND: Vitamin D deficiency can lead to the increased severity and prevalence of metabolic disorders. However, the relationship between levels of 25-hydroxyvitamin D (25(OH)D) and peripheral arterial disease (PAD) is controversial. Therefore, the purpose of our study was to explore the relationship between 25(OH)D levels and PAD in middle-aged and elderly type 2 diabetes mellitus (T2DM) patients in China. METHODS: In this study, a total of 183 patients with T2DM were enrolled and categorized into groups with or without PAD. Clinical and biochemical parameters were assessed, and a Pearson analysis was used to identify a possible association between levels of 25(OH)D and glycated hemoglobin (HbA1c). Some biochemical parameters were also assessed in the T2DM patients with PAD according to vitamin D status. Interactions were also explored among HbA1c control, 25(OH)D levels, and PAD. The possible risk factors for PAD were measured by multivariable logistic regression analyses. RESULTS: Firstly, the parameters including age, HbA1c, and disease duration between T2DM and T2DM+PAD groups showed significantly different. In addition, the frequency of smoking in the group of T2DM patients was significantly less than that in the T2DM patients with the PAD group, while the frequency of well-controlled HbA1c in the patients with T2DM was significantly higher. There is a trend that the levels of 25(OH)D and HbA1c are correlated, but no interactions among vitamin D deficiency, HbA1c control, and PAD were found. However, HbA1c significantly differed between groups with vitamin D deficiency and insufficiency in the T2DM patients with PAD. According to the multivariate logistic regression analyses, the PAD risk factors of T2DM patients were family history of diabetes, smoking, age, disease duration, HbA1c, and LDL. CONCLUSIONS: The findings demonstrate that the deficiency of vitamin D level is not related to PAD, but HbA1c may be linked to the presence of PAD in middle-aged and elderly patients with T2DM in China.

Apolipoprotein E Gene Polymorphism, Glycated Hemoglobin, and Peripheral Arterial Disease Risk in Chinese Type 2 Diabetic Patients.

BACKGROUND: The apolipoprotein E (ApoE) gene polymorphism has been found to influence plasma lipid concentration, and its correlation with peripheral arterial disease (PAD) has been investigated. However, it is unclear whether ApoE is associated with PAD in Chinese type 2 diabetes mellitus (T2DM) patients. Therefore, our study is aimed at investigating the relationship between the ApoE gene polymorphism and PAD in Chinese T2DM patients. METHODS: A total of 192 T2DM patients were divided into two groups: T2DM and T2DM with PAD. The clinical and biochemical parameters were obtained. Polymerase chain reaction was used to identify the genotypes of ApoE. The multivariable logistic regression analysis was used to identify the possible risk factor for PAD. RESULTS: There were no significant differences in the genotype and allele frequencies of ApoE between the T2DM and T2DM with PAD groups. However, the T2DM with PAD group tended to have more ε4/ε4/. CONCLUSIONS: These results demonstrated that there was no evidence of a relationship between ApoE and PAD.

Evaluation of the Role of hsa-mir-124 in Predicting Clinical Outcome in Breast Invasive Carcinoma Based on Bioinformatics Analysis.

PURPOSE: Breast invasive carcinoma (BRCA) is the most common malignant tumor. MiR-124 plays a tumor-suppressive role in human cancer. However, the clinical significance of miR-124 in BRCA remains unclear. The aim of this study was to evaluate the association of hsa-mir-124 expression and the clinicopathological characteristics in BRCA using database analysis. METHODS: The clinical data and expression profiles of hsa-mir-124 were obtained from the cancer genome atlas for BRCA (TCGA_BRCA). Then, the prognostic value of hsa-mir-124 in BRCA was investigated using the Cox Regression test, and the association of hsa-mir-124 and pathology TNM stages and pathologic stages were measured by the Kruskal-Wallis test and Wilcox. test. In addition, the association of hsa-mir-124 and tumor molecular phenotypes was performed using the Chi-Square test. RESULTS: We found that the overall survival of patients with high expression of hsa-mir-124-1 and hsa-mir-124-2 was better than that of patients with low expression of hsa-mir-124-1 and hsa-mir-124-2. And the expression of hsa-mir-124-1, hsa-mir-124-2, and hsa-mir-124-3 was mainly enriched in T1/T2 stages, NO/N1 stages, and M0 stages. Then, the expression of hsa-mir-124-1, hsa-mir-124-2, and hsa-mir-124-3 was negatively associated with tumor lymph node metastasis. Moreover, the expression of hsa-mir-124 was associated with tumor molecular phenotype in breast invasive carcinoma. CONCLUSION: Our findings indicated that hsa-mir-124 expressions were associated with overall survival, TNM stages, pathologic characteristics, and tumor molecular phenotype in BRCA via TCGA_BRCA database, providing a new biomarker and a potential therapeutic target for BRCA patients.

High throughput sequencing identifies breast cancer-secreted exosomal LncRNAs initiating pulmonary pre-metastatic niche formation.

OBJECTIVE: Increasing evidence indicated that cancer-secreted exosomes played an important role in tumor metastasis. However, the function of exosomes in breast cancer pulmonary metastasis remains unknown. The aim of the study was to investigate the role of exosome-derived from breast cancer-secreted long non-coding RNAs (LncRNAs) on pre-metastatic niche formation in pulmonary metastasis. METHODS: Exosomes-derived from breast cancer were separated by ultracentrifugation. The high-throughput sequencing, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to detect and evaluate the differential expression of LncRNAs in lung fibroblasts with exosomes treated. And quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify candidate LncRNAs expression. RESULTS: We found that exosomes-derived from breast cancer induced lung fibroblasts proliferation and migration. In addition, a large number of LncRNAs expression abnormalities were involved in the breast cancer lung metastasis microenvironment. CONCLUSION: Our findings suggested that exosomal LncRNAs facilitated tumor pre-metastatic niche formation and represented a novel mechanistic insight into the molecular mechanism of cancer metastasis microenvironment.

D-dimer as a potential clinical marker for predicting metastasis and progression in cancer.

D-dimer is a widely used biomarker for indicating the activation of coagulation and fibrinolysis, and is reported to serve important roles in cancer progression. The aim of the current retrospective study was to investigate the association of D-dimer plasma level with the development of various cancers. Patients with breast (n=86), gastric (n=317), pancreatic (n=37), colon (n=153) and rectal (n=137) cancers and 92 healthy volunteers were assessed in the present study. Plasma levels of D-dimer in the patients and healthy controls were measured by immunoturbidimetric assays. The association of D-dimer levels with the clinicopathological features of patients were also determined. The plasma levels of D-dimer were significantly higher in patients with breast cancer (P=0.0022), gastric cancer (P<0.0001), pancreatic cancer (P=0.0003), colon cancer (P=0.0001) and rectal cancer (P=0.0028), compared with the healthy controls. It was also determined that the plasma D-dimer levels were positively associated with clinical cancer stage (P<0.05) and metastasis (P<0.05). These findings suggested that the plasma D-dimer level may be used as marker for predicting cancer metastasis and progression.

Exosome-mediated delivery of MALAT1 induces cell proliferation in breast cancer.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Cancer-secreted exosomes have recently been recognized as important mediators of intercellular communication. The aim of this study was to determine the role of exosomal long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in breast cancer progression. MATERIALS AND METHODS: Breast cancer specimens were obtained with informed consent from patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect MALAT1 expression, and cellular proliferation was measured using cell counting kit-8 (CCK-8) assay. RESULTS: MALAT1 was highly expressed in breast cancer tissues and associated with disease progression. Breast cancer exosomes promoted cell proliferation and exosome-mediated MALAT1 to induce cell proliferation. CONCLUSION: These findings indicated that exosomal MALAT1 could regulate cancer progression and represent a novel strategy for overcoming breast cancer.

[Guanylate-binding protein 2 regulates the maturation of mouse dendritic cells induced by ß-glucan].

Objective To investigate the effect of guanylate-binding protein 2 (GBP2) on ß-glucan-induced maturation and immune response of dendritic cells (DCs). Methods RNA-microarray and real time quantitative PCR were used to investigate the change of genes in DCs induced by ß-glucan. Thereafter, DCs were transfected with GBP2 siRNA to knock down the expression of GBP2. Flow cytometry was used to detect the surface markers (CD11c, MHC-II, CD80) on DCs as well as the proliferation of T cells. Cytokines (IL-6, IL-12p70, TNF-α, IL-10) were tested by ELISA. Results The expressions of DC surface markers, including CD11c, MHC- II, CD80, were significantly down-regulated after the cells were transfected with GBP2 siRNA. Moreover, the production of IL-6, IL-12 and TNF-α were also depressed. OVA specific T-cell proliferation decreased when OT-II T cells were co-cultured with GBP2-siRNA transfected-DCs. Conclusion GBP2 can effectively regulate ß-glucan-induced maturation of DCs, thus suppressing the proliferation of T cells.

Routine Hemostasis and Hemogram Parameters: Valuable Assessments for Coagulation Disorder and Chemotherapy in Cancer Patients.

BACKGROUND: The clotting system abnormalities are the common complication in cancer patients. The aim of this retrospective study was to evaluate the coagulation state, clinical features, and treatment in cancer patients by routine tests. METHODS: A total of 2328 patients with different types of cancer were classified as the positive group (n = 1419, including 53 patients with thrombosis) and the negative group (n = 909) based on D-dimer (DD) value. Of the 2328 cases, 354 were admitted for chemotherapy. Hemostasis test and complete blood count (CBC) were performed during treatment or following-up. RESULTS: This study showed that the hypercoagulable state was affected not only by clinical staging (P < 0.0001) but also by metastasis site (P < 0.0001 for bone vs. lung). Compared to negative DD group, the higher fibrinogen level, the extended activated partial thromboplastin time, and prothrombin time interacted markedly with disease clinical stage (P < 0.05) in the positive group. Between positive DD groups with and without thrombus, the significantly statistic difference in white blood cell (WBC) and DD (P < 0.05) rather than in red blood cell (RBC) and platelet count was observed. However, the higher DD level was not correlated with WBC, RBC, and platelet count in the positive DD group. Furthermore, the hypercoagulable plasma profile in cancer patients was moderated 2-3 weeks after chemotherapy (P < 0.05 for first six cycles). CONCLUSIONS: The routine hemostatic parameters and CBC are valuable to assessment for thrombosis and chemotherapy even for disease prognosis.

miR-124 downregulation leads to breast cancer progression via LncRNA-MALAT1 regulation and CDK4/E2F1 signal activation.

The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recently shown to be dysregulated in several cancers. However, the mechanisms underlying the role of MALAT1 in breast cancer remain unclear. Herein, we showed that MALAT1 was aberrantly increased in breast cancer tissues and cells. MALAT1-siRNA inhibited breast cancer cell proliferation and cell cycle progression in vitro and in vivo. Furthermore, MALAT1 acted as an endogenous potent regulator by directly binding to miR-124 and down-regulating miR-124 expression. In addition, MALAT1 reversed the inhibitory effect of miR-124 on breast cancer proliferation and was involved in the cyclin-dependent kinase 4 (CDK4) expression. Taken together, our data highlight the pivotal role of MALAT1 in breast cancer tumorigenesis. Moreover, the present study elucidated the MALAT1-miR-124-CDK4/E2F1 signaling pathway in breast cancer, which might provide a new approach for tackling breast cancer.

ß-glucan restores tumor-educated dendritic cell maturation to enhance antitumor immune responses.

Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) in a tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell-based cancer vaccines can initiate antitumor immune responses, tumor-educated dendritic cells (TEDCs) involved in the tolerance induction have attracted much attention recently. In this study, we investigated the effect of ß-glucan on TEDCs and found that ß-glucan treatment could promote the maturation and migration of TEDCs and that the suppressive function of TEDCs was significantly decreased. Treatment with ß-glucan drastically decreased the levels of regulatory T (Treg) cells but increased the infiltration of macrophages, granulocytes and DCs in tumor masses, thus elicited Th1 differentiation and cytotoxic T-lymphocyte responses and led to a delay in tumor progression. These findings reveal that ß-glucan can inhibit the regulatory function of TEDCs, therefore revealing a novel function for ß-glucan in immunotherapy and suggesting its potential clinical benefit. ß-Glucan directly abrogated tumor-educated dendritic cells-associated immune suppression, promoted Th1 differentiation and cytotoxic T-lymphocyte priming and improved antitumor responses.

Parity and thyroid cancer risk: a meta-analysis of epidemiological studies.

Although observational studies have assessed the relationship between parity and thyroid cancer risk, the findings are inconsistent. To quantitatively assess the association, we conducted a systematic review and meta-analysis. PubMed and Embase were searched up to January 2015. Prospective or case-control studies that evaluated the association between parity and thyroid cancer risk were included. We used the fixed-effects model to pool risk estimates. After literature search, 10 prospective studies, 12 case-control studies and 1 pooled analysis of 14 case-control studies including 8860 patients were identified. The studies had fair methodological quality. Pooled analysis suggested that there was a significant association between parity and risk of thyroid cancer (RR for parous versus nulliparous: 1.09, 95% CI 1.03-1.15; I2=33.4%). The positive association persisted in almost all strata of subgroup analyses based on study design, location, study quality, type of controls, and confounder adjustment, although in some strata statistical significance was not detected. By evaluating the number of parity, we identified that both parity number of 2 versus nulliparous and parity number of 3 versus nulliparous demonstrated significant positive associations (RR=1.11, 95% CI 1.01-1.22; I2=31.1% and RR=1.16, 95% CI 1.01-1.33; I2=19.6% respectively). The dose-response analysis suggested neither a non-linear nor linear relationship between the number of parity and thyroid cancer risk. In conclusion, this meta-analysis suggests a potential association between parity and risk of thyroid cancer in females. However, the lack of detection of a dose-response relationship suggests that further studies are needed to better understand the relationship.

MicroRNA-124 rs531564 Polymorphism and Cancer Risk: A Meta-analysis.

Several studies reported there was a polymorphism (rs531564 C > G) in miR-124 gene. To investigate the MiR-124 rs531564 polymorphism and cancer risk. We conducted a literature search of the Medline, Embase and Wangfang Medicine databases to identify all relevant studies for this meta-analysis. We determined that the miR-124 rs531564 polymorphism was significantly associated with decreased risks of cancers in the allelic model (G vs C, OR=0.71, 95% CI=0.53-0.94, P=0.02), homozygote model (GG vs CC, OR=0.42, 95% CI=0.26-0.66, P=0.0002), dominant model (GG/GC vs CC, OR=0.71, 95% CI=0.51-0.98, P=0.04) and recessive model (GG vs GC/CC, OR=0.43, 95% CI=0.27-0.69, P=0.0004). In an analysis stratified by cervical cancer group, significant associations were observed in the allelic model (G vs C, OR=0.46, 95% CI=0.32-0.66, P<0.0001), and dominant model (GG/GC vs CC, OR=0.45, 95% CI=0.3-0.66, P<0.0001). Subgroup analysis also revealed a decreased risk for esophageal squamous cell carcinoma in the homozygote model (GG vs CC, OR=0.45, 95% CI=0.27-0.75, P=0.002) and recessive model (GG vs GC/CC, OR=0.46, 95% CI=0.28-0.75, P=0.002). This meta-analysis suggests that the miR-124 rs531564 C > G polymorphism is an important risk factor for cancers among the Chinese population.

Parity and endometrial cancer risk: a meta-analysis of epidemiological studies.

The association between parity and endometrial cancer risk is inconsistent from observational studies. We aimed to quantitatively assess the relationship by summarizing all relevant epidemiological studies. PubMed (MEDLINE), Embase and Scopus were searched up to February 2015 for eligible case-control studies and prospective studies. Random-effects model was used to pool risk estimations. Ten prospective studies, 35 case-control studies and 1 pooled analysis of 10 cohort and 14 case-control studies including 69681 patients were identified. Pooled analysis revealed that there was a significant inverse association between parity and risk of endometrial cancer (relative risk (RR) for parous versus nulliparous: 0.69, 95% confidence interval (CI) 0.65-0.74; I(2) = 76.9%). By evaluating the number of parity, we identified that parity number of 1, 2 or 3 versus nulliparous demonstrated significant negative association (RR = 0.73, 95% CI 0.64-0.84, I(2) = 88.3%; RR = 0.62, 95% CI 0.53-0.74, I(2) = 92.1%; and RR = 0.68, 95% CI 0.65-0.70, I(2) = 20.0% respectively). The dose-response analysis suggested a nonlinear relationship between the number of parity and endometrial cancer risk. The RR decreased when the number of parity increased. This meta-analysis suggests that parity may be associated with a decreased risk of endometrial cancer. Further studies are warranted to replicate our findings.

MiR-124 inhibits cell proliferation in breast cancer through downregulation of CDK4.

Studies have shown that microRNAs (miRNAs) are involved in the malignant progression of human cancer. However, little is known about the potential role of miRNAs in breast carcinogenesis. miR-124 expression in breast cancer tissue was measured by quantitative real-time PCR (qRT-PCR). Target prediction algorithms and luciferase reporter gene assays were used to investigate the target of miR-124. Breast cancer cells growth was regulated by overexpression or knockdown miR-124. At the end of the study, tumor-bearing mice were tested to confirm the function of miR-124 in breast cancer. In this study, we demonstrated that the expression of miR-124 was significantly downregulated in breast cancer tissues compared with matched adjacent non-neoplastic tissues. We identified and confirmed that cyclin-dependent kinase 4 (CDK4) was a direct target of miR-124. Overexpression of miR-124 suppressed CDK4 protein expression and attenuated cell viability, proliferation, and cell cycle progression in MCF-7 and MDA-MB-435S breast cancer cells in vitro. Overexpression of CDK4 partially rescued the inhibitory effect of miR-124 in the breast cancer cells. Moreover, we found that miR-124 overexpression effectively repressed tumor growth in xenograft animal experiments. Our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting tumorigenesis by targeting CDK4.

ß-Glucan enhances cytotoxic T lymphocyte responses by activation of human monocyte-derived dendritic cells via the PI3K/AKT pathway.

PURPOSE: To investigate the effects of ß-(1,3/1,6)-d-glucan on dendritic cells (DCs) maturation, cytotoxic T lymphocyte responses and the molecular mechanisms of its transition. METHODS AND RESULTS: Human monocyte-derived DCs were matured using yeast-derived particulate ß-glucan (WGP) or a mix of TNF-α, IL-1ß and IL-6 ("Conv mix"). Multicolor flow cytometry was used to study the DCs phenotype and cytotoxic T-lymphocyte priming and differentiation. ELISA and RT-PCR assays were used to evaluate cytokine production. Western blot was used to investigate the signal pathways. WGP-matured DCs functions were compared with those of Conv mix-matured DCs. WGP-matured DCs expressed higher levels of CD11c, CD86, CD40 and HLA-DR; produced higher levels of pro-inflammatory cytokines; and elicited more CTL priming and differentiation than Conv mix-matured DCs. The PI3K/AKT signaling pathway was involved in WGP-induced dendritic cell maturation. Furthermore, WGP-matured DCs significantly increased tumor-specific CTL responses. CONCLUSION: Excellent ability of yeast-derived particulate ß-glucan to induce DCs maturation and tumor-specific CTL responses explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DCs generated for therapy.