Insulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2) is a post-transcriptional regulatory factor implicated in mRNA localization, stability, and translational control. However, the role of IGF2BP2 regulation in colorectal cancer (CRC) and its underlying mechanism remain elusive. In this study, we found that IGF2BP2 expression is markedly increased in CRC tissues. Notably, IGF2BP2 overexpression strikingly enhanced the proliferation and survival of CRC cells in vitro, whereas its shRNA-mediated silencing resulted in the opposite. Molecular function analyses revealed that IGF2BP2 regulates RAF1 expression through blocking its degradation by miR-195. These results identify IGF2BP2 as a post-transcriptional regulatory mRNAbinding factor that contributes to CRC carcinogenesis.

Obesity and the related liver diseases are prevalent around the world. Although probiotics have been shown to prevent obesity through multiple ways, only few researches investigated the lipid-lowering effects of probiotic Bacillus . Moreover, the limited results consistently suggested that Bacillus regulated genes related to lipogenesis and oxidation, but no further exploration was made. Our previous study revealed that Bacillus amyloliquefaciens SC06 has a potent antioxidant capacity in vitro . The aim of this study is to investigate the effects of SC06 on obesity and the associated liver injury of high-fat diet (HFD)-fed-mice and its underlying mechanism. By feeding normal chow (NC), NC+SC06, HFD, and HFD+SC06 to mice, we found that SC06 improved body weight gain, hepatic steatosis, and glucose metabolism of HFD-mice. Furthermore, SC06 also increased the antioxidant capacity of mice through Nrf2/Keap1 signaling pathway. High-throughput sequencing of 16S rRNA gene showed that HFD changed the gut microbiota dramatically, while HFD+SC06 decreased the ratio of Firmicutes/Bacteroidetes and increased TM7 abundance. More differences were also found in lower taxa. Altogether, SC06 is a potential probiotic that decreases HFD-related lipid accumulation and liver injury via regulating the antioxidant capacity and host gut microbiota.

No abstract

Probiotics are increasingly applied in popularity in both humans and animals. Decades of research has revealed their beneficial effects, including the immune modulation in intestinal pathogens inhibition. Autophagy—a cellular process that involves the delivery of cytoplasmic proteins and organelles to the lysosome for degradation and recirculation—is essential to protect cells against bacterial pathogens. However, the mechanism of probiotics-mediated autophagy and its role in the elimination of pathogens are still unknown. Here, we evaluated Bacillus amyloliquefaciens SC06 (Ba)-induced autophagy and its antibacterial activity against Escherichia coli (E. coli) in murine macrophage cell line RAW264.7 cells. Western blotting and confocal laser scanning analysis showed that Ba activated autophagy in a dose- and time-dependent manner. Ba-induced autophagy was found to play a role in the elimination of intracellular bacteria when RAW264.7 cells were challenged with E. coli. Ba induced autophagy by increasing the expression of Beclin1 and Atg5-Atg12-Atg16 complex, but not the AKT/mTOR signaling pathway. Moreover, Ba pretreatment attenuated the activation of JNK in RAW264.7 cells during E. coli infection, further indicating a protective role for probiotics via modulating macrophage immunity. The above findings highlight a novel mechanism underlying the antibacterial activity of probiotics. This study enriches the current knowledge on probiotics-mediated autophagy, and provides a new perspective on the prevention of bacterial infection in intestine, which further the application of probiotics in food products.

Trichostatin A (TSA) possess histone deacetylase (HDAC) inhibitory potential, can reverse the deactivation of tumor suppressor genes and inhibit tumor cell proliferation. We evaluated the effect of TSA on HDAC expression, tumor cell proliferation, and cancer stem cells (CSCs) activities in pancreatic ductal adenocarnoma (PDAC) cells. The PDAC cell lines MiaPaCa-2 and PANC-1 were distinctly sensitive to TSA, with enhanced apoptosis, compared to SAHA. TSA or SAHA inhibited vimentin, HDACs 1, 7 and 8, upregulated E-cadherin mRNA and protein levels in the PDAC cells, and time-dependently downregulated Oct-4, Sox-2, and Nanog, as well as inhibited PDAC tumorsphere formation. TSA also induces accumulation of acetylated histones, while increasing histone 3 lysine 4 or 9 dimethylation levels in PDAC cells and enhancing the epigenetic activity of SAHA. The anti-CSCs effect of TSA was like that obtained by silencing HDAC-1 or 7 using siRNA, and enhances Gemcitabine activity. Our study highlights the molecular targetability of HDACs 1, 7, and 8, confirm their PDAC-CSCs maintaining role, and demonstrate that compared to SAHA, TSA modulates the epigenetically- mediated oncogenic activity of PDAC-CSCs, and potentiate Gemcitabine therapeutic activity, making a case for further exploration of TSA activity alone or in combination with Gemcitabine in PDAC therapy.