FOXP1 inhibits pancreatic cancer growth by transcriptionally regulating IRF1 expression.

FOXP1, known as a Forkhead-box (FOX) family protein, plays an important role in human tumorigenesis. However, the function and molecular mechanism of FOXP1 in pancreatic cancer (PC) remain unclear. Here, we report that PC patients with FOXP1 overexpression had a higher survival rate compared to patients with low- FOXP1 expression. Additionally, high expression of FOXP1 can markedly inhibit the growth of pancreatic cancer in vivo and in vitro, whereas low expression of FOXP1 effectively promoted the tumorigenesis. Mechanistically, FOXP1 could directly bind the IRF1 promoter, which triggered the transcriptional activity of IRF1. Taken together, FOXP1 suppressed PC growth via IRF1-dependent manner, serving as a potential prognostic biomarker for patients with PC.

The role and mechanism of CARD9 gene polymorphism in diseases.

CARD9 is a cytosolic adaptor in myeloid cells, has a critical role in inflammatory disorders, and provides a protective function against microbial pathogen, especially fungal infection. Recently, CARD9 polymorphisms are of interest, showing a positive correlation with the elevated risk of fungal infection, inflammatory bowel disease, and other autoimmune diseases. Mechanistically, CARD9 polymorphisms impair the activation of RelB, a subunit of non-canonical NF-κB, which lead to the reduced cytokine and chemokine production by innate immune cells. In addition, CARD9 polymorphisms show a defective neutrophil accumulation in infectious sites. Furthermore, CARD9 polymorphisms could alter the composition of the gut microbiome. In this review, we summarize the latest findings of CARD9 polymorphisms with respect to inflammatory diseases.

miR-212 and mTOR form a regulation loop to modulate autophagy in colorectal adenoma HT-29 cells.

Autophagy is a conserved lysosomal degradation pathway that regulates cell survival and death in order to maintain cellular homeostasis. Dysfunctional autophagy is associated with different types of cancer, making it an attractive therapeutic target. Mammalian target of rapamycin (mTOR) signaling negatively regulates autophagy and suppresses the efficacy of certain cancer therapeutic agents. NVP-BEZ235 is a dual inhibitor of the PI3K/mTOR signaling pathway and exhibits anti-cancer activities; it also induced autophagy and inhibited proliferation in colorectal adenoma HT-29 cells. Colorectal adenoma and colorectal cancer have been recently shown to have elevated levels of miR-212. In the current study, we examined the role of miR-212 in NVP-BEZ235-induced autophagy in HT-29 cells. NVP-BEZ235 at the concentration as low as of 1 nM effectively induced autophagy and dose-dependently inhibited the expression of microRNA-212 (miR-212) whereas mTOR activator MHY1485 elevated the miR-212 expression. Transfection of miR-212 mimics inhibited autophagy whereas miR-212 inhibitors promoted autophagy as assessed by the LC3B-I conversion to LC3B-II and the expression levels of beclin-1. Furthermore, miR-212 mimics activated mTOR whereas miR-212 inhibitors suppressed mTOR activation as shown by the levels of phospho-mTOR. miR-212 mimics further enhanced the effect of NVP-BEZ235 in reducing the viability of HT-29 cells. Our data support that miR-212 is a target of mTOR signaling as well as an activator of mTOR to negatively regulate autophagy. Thus, miR-212 and mTOR signalings may form a positive regulation loop in maintaining cellular homeostasis. This study warrants further investigation of miR-212 as an effective target of autophagy-based cancer therapeutic strategies.