EXOSC2 Mediates the Pro-tumor Role of WTAP in Breast Cancer Cells via Activating the Wnt/ß-Catenin Signal.

BC (breast cancer) is the leading cause of cancer death in women. Exosome component 2 (EXOSC2), an RNA exosome component, is elevated in BC tissues and may relate to BC carcinogenesis. In this work, the high EXOSC2 expression was correlated with TNM (Tumor Node Metastasis) stage. Moreover, overexpression of EXOSC2 enhanced tumorigenic capacity of BC cells via facilitating cell proliferation and cell cycle progression, increasing migration and angiogenesis, as well as exacerbating xenograft formation in vivo. Whereas, EXOSC2 knockdown showed anti-cancer effects, including inhibition of cell proliferation and angiogenesis. Mechanistically, EXOSC2 activated the wnt/ß-catenin pathway, which was also abolished by EXOSC2 knockdown. In addition, there were m6A methylation modification sites in the mRNA of EXOSC2. WTAP (Wilms tumor 1-associated protein) bound to EXOSC2 mRNA and increased its m6A methylation, resulting in extending the half-life of EXOSC2 mRNA. Luciferase data also confirmed that WTAP enhanced EXOSC2 mRNA stability through binding with the 3'-UTR containing m6A sites. Furthermore, WTAP silencing exhibited cancer-inhibiting effects on cell viability, cell cycle progression and tube formation, which was effectively reversed by EXOSC2 overexpression. In conclusion, our results demonstrate that EXOSC2 promotes the malignant behaviors of BC cells via activating the wnt/ß-catenin pathway. In addition, EXOSC2 mediates the function of WTAP which contributes to the m6A modification of EXOSC2. Totally, this study suggested that EXOSC2 mediated the pro-tumor role of WTAP via activating the wnt/ß-catenin signal.

[Research Progress of Cytokines in the Prognosis of Acute Myeloid Leukemia --Review].

At present, acute myeloid leukemia (AML) is mainly treated with combination medication, high-dose, and early intensification. The treatment has achieved good results, but the long-term treatment effect is still not satisfactory. Studies have shown that the different levels of cytokine expression in AML patients can help AML risk stratification, search for treatment directions and predict the prognosis. It has been confirmed that the expression of IL-1ß, IL-6, TNF-α, and TGF-ß1 are increased in AML patients, and they all indicate a poor prognosis. However, IL-8, IFN-γ, and CCL5 have great research value in chemotherapy resistance and improvement of treatment effect. This article reviews the research progress of cytokine biomarkers in the prognosis of AML patients.

Insights into the interaction of human serum albumin and carbon dots: Hydrothermal synthesis and biophysical study.

Nitrogen and sulfur co-doped carbon dots (N,S-CDs) have been widely studied with high quantum yield (QY). The experimental conditions of three different N,S-CDs were optimized. Emission peak position of three different N,S-CDs shown almost remains unchanged or obvious excitation-dependent PL properties, that was likely owed to size distribution. In order to discuss the N,S-CDs stability of photoluminescence property in environment, various experiments such as the photostability, different pH, ionic strengths and temperature were designed. To sum up, three different N,S-CDs exhibited discrepancy property. Molecular interaction of three different N,S-CDs were produced via vary carbon source with human serum albumins have been investigate by various methods. The quenching mechanism, thermodynamic and kinetic parameters, binding sites, electrochemical behavior of three different N,S-CDs with human serum albumins have some different, but conformational change of three different N,S-CDs with human serum albumins alike. The molecular docking had successful applied to study the N,S-CDs interaction with HSA. Different N,S-CDs possessed various characteristic that will have different quenching mechanism when they interaction with human serum albumin, study the mechanism of action at molecular level will help people to choose suitable CDs to apply in nanomedical.

Nomogram for predicting the risk of bone metastasis in breast cancer: a SEER population-based study.

BACKGROUND: Bone is the most common metastasis site of breast cancer. The prognosis of bone metastasis is better than other distant metastases, but patients with skeletal related events (SREs) have a poor quality of life, high healthcare costs and low survival rates. This study aimed to establish an effective nomogram for predicting risk of bone metastasis of breast cancer. METHODS: The nomogram was built on 4,895 adult/female/primary invasive breast cancer patients with complete clinicopathologic information, captured by the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Five biological factors (age, grade, histologic type, surgery of breast lesions and subtypes) were assessed with logistic regression to predict the risk of bone metastases. The predictive accuracy and discriminative ability of the nomogram were determined by the Receiver Operating Characteristic (ROC) curves and the calibration plot. Results were validated on a separate 2,093 cohort using bootstrap resampling from 2010 to 2015 as an internal group and a retrospective study on 120 patients in the First Affiliated Hospital of China Medical University from 2010 to 2014 at the same situation as an external group. RESULTS: On multivariate logistic regression of the primary cohort, independent factors for bone metastases were age, grade, histologic type, surgery of breast lesions and subtypes, which were all selected into the nomogram. The calibration plot for probability of incidence showed good agreement between prediction by nomogram and two observations. The ROC curves presented a good statistical model for risk of bone metastasis, and the corresponding AUC value of the development group, internal validation group and external validation group were 0.678, 0.689 and 0.704 respectively. CONCLUSIONS: The proposed nomogram resulted in more-accurate prognostic prediction for breast cancer patients with bone metastases.

Hierarchically Nanostructured Fe3O4/C Composite as a Promising Magnetic Targeted Drug Nanocarrier.

Nanostructured Fe3O4/C composites are very attractive for high-performance magnetic targeted drug carriers. Herein, Fe3O4/C composite nanospheres with good dispersity are prepared by a simple one-step hydrothermal synthesis and subsequent heat treatment in Ar. The composite nanospheres consist of clustered primary nanoparticles, and exhibit a hierarchical architecture with a high specific surface area of 119.3 m² g-1. The Fe3O4/C composite nanospheres show a high saturation magnetization value of 101 emu g-1 and good biocompatibility. In particular, the composite nanospheres deliver a large loading content (85.8%) of epirubicin hydrochloride (EPI), resulting from their unique composition and microstructure. More importantly, the release of EPI from the EPI-loaded magnetic carrier (Fe3O4/C-EPI) may be enhanced by both a slightly acidic environment and a rotating magnetic field induced by a simple motor-driven magnet system. The above favorable properties make the hierarchical Fe3O4/C composite sample a promising candidate for magnetic targeting nanocarriers of EPI.

Overexpression of LncRNA HOTAIR is Associated with Poor Prognosis in Thyroid Carcinoma: A Study Based on TCGA and GEO Data.

The role of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in thyroid carcinoma (TC) remains unclear. The current study was aimed to assess the clinical value of HOTAIR expression levels in TC based on publically available data and to evaluate its potential signaling pathways. The expression data of HOTAIR and clinical information concerning TC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Furthermore, 3 online biological databases, Starbase, Cbioportal, and Multi Experiment Matrix, were used to identify HOTAIR-related genes in TC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Panther pathway analyses were then undertaken to study the most enriched signaling pathways in TC (EASE score<0.1, Bonferroni<0.05). The TCGA results demonstrated that the expression level of HOTAIR in TC tissues was significantly increased compared with non-cancerous tissues (p<0.001). HOTAIR over-expression was significantly associated with poor survival in TC patients (p=0.03). Meta-analyses of GEO datasets revealed a trend consistent with the above results on HOTAIR expression levels in TC (SMD=0.23; 95%CI, 0.00-0.45; p=0.047). Finally, the results of functional analysis for HOTAIR-related genes indicated that HOTAIR might participate in tumorigenesis via the Wnt signaling pathway. In conclusion, our study demonstrates that HOTAIR may be involved in thyroid carcinogenesis, and the over-expression of HOTAIR could act as a biomarker associated with a poor outcome in TC patients. Moreover, the Wnt signaling pathway may be the key pathway regulated by HOTAIR in TC.

[RNAi-mediated gene silencing of livin synergistic with epirubicin enhance apoptosis of human breast cancer cells].

OBJECTIVE: To observe the effects of silencing of livin gene expression combined with anthracycline chemotherapy on the apoptosis of human breast cancer cells. METHODS: Double stranded RNA (dsRNA) targeting the livin gene was chemically synthesized in vitro and transfected into human breast cancer cells of the line ZR-75-30 mediated by lipofectamine 2000. The transfection efficiency was observed by fluorescence confocal microscopy. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression of livin at mRNA and protein levels. ZR-75-30 cells transfected with dsRNA targeting livin for 24 h were treated with 50 microg/ml epirubicin for 12 h, flow cytometry was used to detect the apoptosis rate of the cells. RESULTS: The livin mRNA expression rates of the livin-siRNA transfected group was (29.68 +/- 2.7)%, with an inhibitory rate of 53.66%, significantly lower than those of the negative control and blank control groups [(52.01 +/- 2.9)% and (51.95 +/- 3.1)% respectively, both P < 0.01]. The livin protein expression rate of the livin-siRNA group was (27.80 +/- 2.1)%, significantly lower than those of the negative control siRNA group and blank control group [(53.80 +/- 3.0)% and (55.12 +/- 2.8)% respectively, both P < 0.01]. 36 h after the treatment of siRNA against livin combined with epirubicin the apoptosis rate was (15.18 +/- 0.05)%, significantly higher than those of the negative control group and blank control group [(2.78 +/- 0.08)% and (2.65 +/- 0.12)% respectively, both P < 0.01]. CONCLUSIONS: Sequence specific siRNA targeting livin synergistic with epirubicin is capable of enhancing the apoptosis rate of human breast cancer cells. Silencing of livin gene expression with siRNA combined with anthracycline chemotherapy may hold great promise as a novel therapy for livin expressing breast cancer.