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The sensitivity of cells to chemotherapeutic agents has a major effect on disease outcome in breast cancer patients. Unfortunately, there are numerous factors involved in the regulation of chemosensitivity, and the mechanisms need to be further investigated. Autophagy/Beclin 1 regulator 1 (Ambra1) is a key protein in the crosstalk between autophagy and apoptosis. It controls the switch between these two processes, which determines whether cells survive or die. Induction of apoptosis is the primary mechanism by which most chemotherapeutic drugs eliminate cancer cells. Recently, Ambra1 has been shown to modulate paclitaxel-induced apoptosis in breast cancer cells via the Bim/mitochondrial pathway, thereby modifying the sensitivity of cells to paclitaxel. However, how Ambra1 regulates Bim expression remains unclear. Here, we further confirmed that Bim plays an indispensable role in Ambra1's regulation of apoptosis and chemosensitivity in breast cancer cells. Furthermore, Ambra1 was found to regulate Bim expression at the transcriptional level through the Akt-FoxO1 pathway. Therefore, we propose a novel pathway, Ambra1-Akt-FoxO1-Bim, which regulates apoptosis and chemosensitivity in breast cancer cells. Thus, Ambra1 may represent a potential target for breast cancer treatment.

Cancer cells often evade apoptosis induced by anti-cancer drugs, which reduces the efficacy of the drugs. Autophagy/Beclin 1 regulator 1 (Ambra1) is a crucial proautophagic protein. It also plays an important role in the execution of apoptosis. However, the mechanism by which Ambra1 regulates apoptosis has not been fully clarified. Moreover, whether Ambra1 participates in the regulation of paclitaxel-induced apoptosis in breast cancer cells is not clear. Here, we show that Ambra1 inhibits paclitaxel-induced apoptosis in breast cancer cells. Moreover, Bim and mitochondria are key effectors of Ambra1 in this process. Thus, Ambra1 is a protein that makes breast cancer cells resistant to apoptosis by modulating the Bim/mitochondrial pathway. Therefore, Ambra1 may be a potential target for the treatment of breast cancer.

&beta, 1,3 xylanase is an important enzyme in the biorefinery process for some algae. The discovery and characterization of new &beta, 1,3 xylanase is a hot research topic. In this paper, a novel &beta, 1,3 xylanase (Xyl88) is revealed from the annotated genome of Flammeovirga pacifica strain WPAGA1. Bioinformatic analysis shows that Xyl88 belongs to the glycoside hydrolase 26 (GH26) with a suspected CBM (carbohydrate-binding module) sequence. The activity of rXyl88 is 75% of the highest enzyme activity (1.5 mol/L NaCl) in 3 mol/L NaCl buffer, which suggests good salt tolerance of rXy188. The optimum reaction temperature in the buffer without NaCl and with 1.5 mol/L NaCl is 45 &deg, C and 55 &deg, C, respectively. Notably, the catalytic efficiency of rXyl88 (kcat/Km) is approximately 20 higher than that of the thermophilic &beta, 1,3 xylanase that has the highest catalytic efficiency. Xyl88 in this study becomes the most efficient enzyme ever found, and it is also the first reported moderately thermophilic and salt-tolerant &beta, 1,3 xylanase. Results of molecular dynamics simulation further prove the excellent thermal stability of Xyl88. Moreover, according to the predicted 3D structure of the Xyl88, the surface of the enzyme is distributed with more negative charges, which is related to its salt tolerance, and significantly more hydrogen bonds and Van der Waals force between the intramolecular residues, which is related to its thermal stability.

The sensitivity of breast cancer cells to epirubicin (EPI) is closely related to the efficacy of the drug and the prognosis of patients. A growing body of research has suggested that autophagy is involved in the treatment of a variety of cancers, including breast cancer, and modifies the sensitivity of anticancer drugs. However, the mechanism by which autophagy participates in cancer therapy and modulates drug sensitivity has not been fully elucidated. In this study, we showed that the expression of Autophagy/Beclin 1 regulator 1 (Ambra1), a key protein of autophagy, was negatively correlated with EPI sensitivity in breast cancer cells. In addition, it altered the sensitivity of breast cancer cells to EPI by regulating EPI-induced autophagy. As a potential mechanism, we demonstrated that autophagy-related protein 12 (ATG12) was a downstream protein that Ambra1-regulated EPI-induced autophagy. Therefore, Ambra1 plays an important role in regulating the sensitivity of breast cancer cells to EPI. And the regulatory effect of Ambra1 on EPI sensitivity is achieved through the regulation of autophagy by targeting ATG12. Overall, we propose a novel mechanism by which autophagy modulates the sensitivity of breast cancer cells to EPI. ATG12 is a novel targeting protein of Ambra1 in regulating EPI-induced autophagy. In addition, the important role of Ambra1 in modulating the sensitivity of breast cancer cells to EPI is confirmed in vivo. This finding indicates that Ambra1 might be a target for developing breast cancer treatments.

Background MiR-182-5p, as a member of miRNA family, can be detected in lung cancer and plays an important role in lung cancer. To explore the clinical value of miR-182-5p in lung squamous cell carcinoma (LUSC) and to unveil the molecular mechanism of LUSC. Methods The clinical value of miR-182-5p in LUSC was investigated by collecting and calculating data from The Cancer Genome Atlas (TCGA) database, the Gene Expression Omnibus (GEO) database, and real-time quantitative polymerase chain reaction (RT-qPCR). Twelve prediction platforms were used to predict the target genes of miR-182-5p. Protein-protein interaction (PPI) networks and gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore the molecular mechanism of LUSC. Results The expression of miR-182-5p was significantly over-expressed in LUSC than in non-cancerous tissues, as evidenced by various approaches, including the TCGA database, GEO microarrays, RT-qPCR, and a comprehensive meta-analysis of 501 LUSC cases and 148 non-cancerous cases. Furthermore, a total of 81 potential target genes were chosen from the union of predicted genes and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in pathways related to biological processes. PPIs revealed the relationships between these genes, with EPAS1, PRKCE, NR3C1, and RHOB being located in the center of the PPI network. Conclusions MiR-182-5p upregulation greatly contributes to LUSC and may serve as a biomarker in LUSC.

The present study investigated the sensitization of 5-fluorouracil (5-FU)-resistant colon cancer cells in vitro, using oxymatrine, a Chinese herb, and a quinolizidine alkaloid compound extracted from the root of Sophora flavescens. The HCT-8 colon cancer cell line and its 5-FU-resistant subline HCT-8/5-FU were treated with 5-FU and oxymatrine, alone or in combination, at various doses. The cells were subsequently assessed for changes in cell viability, apoptosis and morphology and analyzed by fluorescence microscopy and western blotting. The data demonstrated that HCT-8/5-FU markedly increased the dose of 5-FU required for the suppression of tumor cell viability (78.77±1.90 µg/ml vs. 9.20±0.96 µg/ml in parental HCT-8 cells), whereas HCT-8/5-FU induced the tumor cell epithelial-mesenchymal transition (EMT). By contrast, oxymatrine alone and in combination with 5-FU altered HCT-8/5-FU cell morphology, apoptosis and EMT phenotypes. The combination of oxymatrine and 5-FU reduced the protein expression of snail family transcriptional repressor 2 and vimentin, phosphorylated p65 and induced the expression of E-cadherin, by inhibiting the nuclear factor κB (NF-κB) signaling pathway. In conclusion, the data from the present study demonstrated that EMT was associated with 5-FU chemoresistance in HCT-8/5-FU colon cancer cells, and that oxymatrine treatment was able to reverse such resistance. Oxymatrine may regulate tumor cell EMT and inactivate the NF-κB signaling pathway, and may therefore serve as a potential therapeutic drug to reverse 5-FU resistance in colon cancer cells.