BackgroundThe flavonoid baicalein, a historically used Chinese herbal medicine, shows a wide range of biological and pharmaceutical effects, among which its potent antitumor activity has raised great interest in recent years. However, the molecular mechanism involved in the antimetastatic effect of baicalein remains poorly understood. This study aimed to verify the inhibitory effects of baicalein on metastasis of MDA-MB-231 human breast cancer cells both in vitro and in vivo, as well as to investigate the related mechanisms.MethodsMTT assay was used to examine the inhibition of baicalein on proliferation of MDA-MB-231 cells. Wound healing assay and the in vitro invasion assay was carried out to investigate the effects of baicalein on migration and invasion of MDA-MB-231 cells, respectively. In order to explore the effects of baicalein on tumor metastasis in vivo, xenograft nude mouse model of MDA-MB-231 cells was established. Animals were randomly divided into four groups (control, therapy group, and low-dose and high-dose prevention group, n=6), and treated with baicalein as designed. Following sacrifice, their lungs and livers were collected to examine the presence of metastases. qRT-PCR and Western blot were performed to study the effects of baicalein on expression of SATB1, EMT-related molecules, and Wnt/β-catenin signaling components of MDA-MB-231 cells as well as the metastatic tissue. Effects of baicalein on the expression of target proteins in vivo were also analyzed by immunohistochemistry.ResultsOur results indicated that baicalein suppressed proliferation, migration, and invasion of MDA-MB-231 cells in a time- and dose-dependent manner. Based on assays carried out in xenograft nude mouse model, we found that baicalein inhibited tumor metastasis in vivo. Furthermore, baicalein significantly decreased the expression of SATB1 in MDA-MB-231 cells. It suppressed the expression of vimentin and SNAIL while enhancing the expression of E-cadherin. Baicalein also downregulated the expression of Wnt1 and β-catenin proteins and transcription level of Wnt/β-catenin-targeted genes.ConclusionOur results demonstrate that baicalein has the potential to suppress breast cancer metastasis, possibly by inhibition of EMT, which may be attributed to downregulation of both SATB1 and the Wnt/β-catenin pathway. Taken together, baicalein may serve as a promising drug for metastasis treatment of breast cancer.

BackgroundmiR-126 is a key regulator of oncogenic processes. It is functionally linked to cellular proliferation, survival and migration. Vascular endothelial growth factor A (VEGF-A), which is regarded as a tumorgenesis activator, could directly target miR-126 in several tumors. However, the mechanism in esophageal cancer remains unclear.Methods and resultsIn this study, the expression of miR-126 and VEGF-A were assessed in esophageal cancer tissues and esophageal cancer cell lines. We found that miR-126 has significantly lower expression in esophageal cancer tissues and esophageal cancer cell lines than in healthy tissues, while the expression of VEGF-A is high. Luciferase reporter assays were performed to investigate the relationship between VEGF-A and miR-126. We confirmed that VEGF-A is a target for miR-126. Furthermore, the proliferation of esophageal cancer cells with miR-126 overexpression and miR-126 knockdown was monitored using the MTT assay. The results showed that miR-126 could inhibit esophageal cancer cell proliferation in vitro. The effect of miR-126 was also detected in BALB/c nude mice with transplanted esophageal cancer cells. In vivo study showed that tumor growth was significantly suppressed by miR-126 overexpression.ConclusionsWe believe that restoring miR-126 levels may be a promising therapeutic approach in cases of esophageal cancer.

The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and enzymatic O-linked glycosylation (O-GlcNAcation) through the addition of O-linked-β-N-acetylglucosamine in esophageal squamous cell carcinoma. OGT expression and O-GlcNAcation in 40 samples from patients with esophageal squamous cell carcinoma was detected by immunohistochemical staining with anti-OGT antib ody and O-GlcNAc-specific antibody RL2, respectively. The relationship between pathological and clinical factors of patients was analyzed. We found that the expression of OGT was higher in esophageal squamous cell carcinoma samples compared to the normal tissues. RL2 antibody level was positively correlated with OGT expression, and the metastasis of lymph node, which means the level of O-GlcNAcation was high and related to the metastasis of lymph node in esophageal squamous cell carcinoma. In conclusion, OGT activation is the main reason for promoting the level of O-GlcNAcation in esophageal squamous cell carcinoma. O-GlcNAcylation may play an important role in esophageal squamous cell carcinoma.

MicroRNAs (miRNAs) play critical roles in the development and progression of various cancers, including non-small-cell lung cancer (NSCLC). Studies have suggested that miR-330-5p is involved in the progression of several cancers. However, the role of miR-330-5p in NSCLC remains unclear. We investigated the effect on and mechanism of miR-330-5p in the progression of NSCLC. We found that miR-330-5p was significantly downregulated in NSCLC tissues and cell lines as detected by real-time quantitative polymerase chain reaction (RT-qPCR). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), bromodeoxyuridine (BrdU), colony formation and cell cycle assays showed that overexpression of miR-330-5p markedly inhibited cell growth. Annexin V-FITC/PI and caspase-3 activity assays showed that overexpression of miR-330-5p significantly promoted cell apoptosis of NSCLC cells. Bioinformatics analysis and dual-luciferase reporter assays confirmed NIN/RPN12 binding protein 1 (NOB1) as a target gene of miR-330-5p. RT-qPCR and Western blot analysis showed that overexpression of miR-330-5p inhibited the expression of NOB1 as well as cyclin D1 and cyclin-dependent kinase 4 in NSCLC cells. Moreover, overexpression of NOB1 markedly reversed the miR‑330-5p-mediated inhibitory effect on NSCLC cell growth. Correlation analysis showed that miR‑330-5p expression was inversely correlated with NOB1 mRNA expression in NSCLC tissues. Taken together, our results indicate that miR-330-5p inhibits NSCLC cell growth through downregulation of NOB1 expression. Our study suggests that miR-330-5p may serve as a potential therapeutic target for the treatment of NSCLC.

DEAD (Asp-Glu-Ala-Asp) box protein 5 (DDX5), a prototypical member of the DEAD/H-box protein family, has been involved in several human malignancies. However, the expression and biological role of DDX5 in esophageal cancer (EC) remain largely unknown. In this study, we examined the role of DDX5 in regulating EC cell proliferation and tumorigenesis and explored its possible molecular mechanism. We found that DDX5 was overexpressed in human EC cell lines. In addition, knockdown of DDX5 significantly inhibited the proliferation of EC cells in vitro and the growth of EC xenografts in vivo. Knockdown of DDX5 also suppressed the migration/invasion and epithelial-to-mesenchymal transition (EMT) phenotype in EC cells. Furthermore, we observed that knockdown of DDX5 inhibited the expression of β-catenin, c-Myc, and cyclin D1 in EC cells. In conclusion, our findings provide the first evidence that siRNA-DDX5 inhibited the proliferation and invasion of EC cells through suppressing the Wnt/β-catenin signaling pathway. Therefore, DDX5 may be a novel potential therapeutic target for the prevention and treatment of EC.