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Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction–oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.

Family with sequence similarity (FAM46) proteins are newly identified metazoan-specific poly(A) polymerases (PAPs). Although predicted as Gld-2-like eukaryotic non-canonical PAPs, the detailed architecture of FAM46 proteins is still unclear. Exact biological functions for most of FAM46 proteins also remain largely unknown. Here, we report the first crystal structure of a FAM46 protein, FAM46B. FAM46B is composed of a prominently larger N-terminal catalytic domain as compared to known eukaryotic PAPs, and a C-terminal helical domain. FAM46B resembles prokaryotic PAP/CCA-adding enzymes in overall folding as well as certain inter-domain connections, which distinguishes FAM46B from other eukaryotic non-canonical PAPs. Biochemical analysis reveals that FAM46B is an active PAP, and prefers adenosine-rich substrate RNAs. FAM46B is uniquely and highly expressed in human pre-implantation embryos and pluripotent stem cells, but sharply down-regulated following differentiation. FAM46B is localized to both cell nucleus and cytosol, and is indispensable for the viability of human embryonic stem cells. Knock-out of FAM46B is lethal. Knock-down of FAM46B induces apoptosis and restricts protein synthesis. The identification of the bacterial-like FAM46B, as a pluripotent stem cell-specific PAP involved in the maintenance of translational efficiency, provides important clues for further functional studies of this PAP in the early embryonic development of high eukaryotes.

Non-small cell lung cancer (NSCLC) accounts for >80% of all cases of lung cancer and can be divided into lung adenocarcinoma (LAC), large-cell carcinoma (LCC), and squamous cell carcinoma (SCC). Accumulating evidence suggests that MTSS1, which is a newly discovered protein associated with tumor progression and metastasis, may have differential roles in cancer malignancy. As it has been demonstrated that MTSS1 is overexpressed in NSCLC and may be an independent prognostic factor in patients with SCC, the present study explored the differential roles of MTSS1 in the invasion and proliferation of different subtypes of NSCLC. Stable overexpression and knockdown of MTSS1 was performed in human NSCLC H920 (LAC), H1581 (LCC) and SW900 cell lines (SCC), and western blot, cell invasion, proliferation and FAK activity analyses were used to investigate the effects. Overexpression of MTSS1 enhanced the invasion and proliferation abilities of H920 and H1581 cells, and these effects were abolished by treatment with selective FAK inhibitor 14, which did not affect the expression of MTSS1. Notably, overexpression of MTSS1 inhibited invasion and proliferation in SW900 cells, and this effect was enhanced by the selective FAK inhibitor. Knockdown of MTSS1 decreased the invasion and proliferation abilities of H920 and H1581 cells, whereas knockdown increased invasion and proliferation in SW900 cells. Furthermore, while overexpression of MTSS1 induced FAK phosphorylation and activity in H920 and H1581 cells, MTSS1 overexpression inhibited FAK phosphorylation/activity in SW900 cells. Knockdown of MTSS1 decreased FAK phosphorylation/activity in H920 and H1581 cells, whereas knockdown increased these processes in SW900 cells. To the best of our knowledge, the present study was the first to demonstrate that MTSS1 has differential roles in various subtypes of NSCLC, acting via a FAK-dependent mechanism. The results indicated that MTSS1 may enhance invasion and proliferation in LAC and LCC cells, whereas MTS11 inhibits these processes in SCC cells. These findings provide novel insight into the functional role of MTSS1 in cancer and may help elucidate therapeutic strategies for the treatment of various types of cancer.

Clinical studies have reported evidence for the involvement of octamer‑binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelial‑mesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the β‑catenin/E‑cadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and N‑cadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting β‑catenin/E‑cadherin complex degradation and regulating nuclear localization of β‑catenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the β‑catenin/E‑cadherin complex was regulated by Oct4 during the process of EMT.

The objective of this work is to study on the preparation of peanut protein peptide by lactobacillus solid state fermentation method and to provide a theoretical basis for further investigating peanut meal special protein material product. Results indicated that the soluble nitrogen concentration of peanut protein peptide could reach 70.92mg/ml, 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) and hydroxyl free radicals scavenging rates were 95.00% and 86.28%, respectively, under the following optimum conditions: addition of nutrient salt solution volume of 25ml, lactobacillus liquid volume of 5ml, temperature of 25.0 °C, and time of 72h. Peanut protein peptide had good antioxidant activities.

The objective of this work is to study on preparation of peanut protein peptide by bacillus subtilis solid state fermentation method. Results indicated that soluble nitrogen concentration of protein peptide could reach 122.86mg/mL, 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) and hydroxyl free radicals scavenging rates were 85.22% and 84.88%, respectively, under the following optimum conditions: nutrient salt solution of 16.3mL, bacterial suspension volume of 3.8mL, temperature of 45°C, and time of 41h. IC50values for scavenging of DPPH, hydroxyl and superoxide anion free radicals rates, iron and copper ion chelating rates, inhibition rate of anti-lipid peroxidation were 2.88mg/mL, 4.63mg/mL, 1.22mg/mL, 0.04mg/mL, 0.94mg/mL, 3.78mg/mL, respectively. When absorbance value of iron and molybdenum reduction capacities was 0.5, the required protein peptide concentrations were 7.28mg/mL and 1.85mg/mL, respectively.

Previous studies have identified a variety of microRNAs (miRNAs) that have important roles in cancer progression, particularly in tumor invasion and metastasis. Downregulation of miR‑145 was reported to occur in various types of human cancer; however, the role of miR‑145 in lung cancer metastasis and its potential mechanisms of action remain to be elucidated. The present study aimed to investigate the effects of miR‑145 on metastasis and epithelial‑mesenchymal transition (EMT) in A549 human lung adenocarcinoma cells. In addition, the underlying mechanisms by which miR‑145 regulates EMT were examined. The miR‑145 mimic was transfected into A549 cells; cell invasion and adhesion assays were then performed in order to investigate cell metastasis, and western blot analysis was used to examine the expression of EMT markers. In order to further examine the underlying mechanisms by which miR‑145 regulates EMT, a luciferase reporter assay was performed to determine whether miR‑145 targeted Oct4. In addition, the expression of Wnt3a and β‑catenin in A549 cells was measured following transfection with small hairpin RNA‑Oct4. To the best of our knowledge, the results of the present study demonstrated for the first time, that miR‑145 inhibited lung cancer cell metastasis and EMT via targeting the Oct4 mediated Wnt/β‑catenin signaling pathway.