Avenanthramide C induces cellular senescence in colorectal cancer cells via suppressing ß-catenin-mediated the transcription of miR-183/96/182 cluster.

Cellular senescence is representing a potential anticancer therapeutic arsenal. Avenanthramide C (AVN C), as a signature compound of oats, exhibits antioxidant, anti-inflammatory, anti-atherosclerotic, and anti-tumor activities. However, the relationship between AVN C and cellular senescence in tumors remains largely unclear. Here, we elucidated that AVN C treatment predisposed colorectal cancer cells to senescent phenotype confirmed by flattened and enlarged shape characteristics, elevated senescence-associated ß-galactosidase (SA-ß-Gal) activity, and G1 phase arrest. Furthermore, AVN C triggered cellular senescence via transcriptionally repressing miR-183/96/182 cluster and subsequently reduced the levels of mature miR-183, -96, and -182. Mechanistically, AVN C exerted its senescence induction by attenuating ß-catenin-mediated transactivation of miR-183/96/182 cluster to unleash its common target FOXO1 and two other targets, FOXO3 and SMAD4, which subsequently foster the p21 and p16 expression. In addition, AVN C is also noted to facilitate p53-mediated p21 transactivation via suppressing ß-catenin. Collectively, we identified a novel mechanism of ß-catenin/miR-183/96/182 cluster/FOXO1 mediated-CRC cellular senescence that entails that AVN C serves as an auxiliary agent for CRC treatment.

Chemerin/CMKLR1 ameliorates nonalcoholic steatohepatitis by promoting autophagy and alleviating oxidative stress through the JAK2-STAT3 pathway.

Nonalcoholic steatohepatitis (NASH) is a global public health challenge. Overwhelmed oxidative stress and impaired autophagy play an important role in the progression of NASH. Chemerin is an adipokine that has attracted much attention in inflammation and metabolic diseases. This study aimed to examine the effects of chemerin in NASH and its association with oxidative stress and autophagy. In this study, chemerin was found to significantly ameliorate high-fat diet (HFD) induced NASH, marked by decreased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α), decreased insulin resistance (IR) and leptin resistance (LR), and improved liver lesions. Besides, chemerin prevented enhanced oxidative stress in NASH mice by regulating the antioxidant defense system (MDA downregulation and upregulation of superoxide dismutase (SOD)). Moreover, chemerin contributed to the alleviation of NASH through autophagy activation (p62 downregulation, and upregulation of beclin-1 and LC3). Furthermore, these effects were related to increased phosphorylation of JAK2-STAT3 stimulated by chemerin, which could be inhibited by the CMKLR1 specific inhibitor α-NETA. In conclusion, excess chemerin highly probably ameliorated NASH by alleviating oxidative stress and promoting autophagy, the mechanism responsible for this process was related, at least in part, to the increased phosphorylation of JAK2-STAT3 stimulated by chemerin/CMKLR1. Rh-chemerin may represent promising therapeutic targets in the treatment of NASH.

MiR-223-3p promotes the proliferation, invasion and migration of colon cancer cells by negative regulating PRDM1.

Colon cancer is one of the most common malignancies worldwide, while the molecular mechanism remains largely unknown. miR-223-3p plays an important role in cancer development. Here, we found that miR-223-3p was up-regulated in 30 cases of colon cancer tissues as compared with their adjacent normal tissues. Lentivirus-mediated miR-223-3p over-expression promoted the proliferation, colony formation, migration and invasion of colon cancer cells. Inverse results were observed in miR-223-3p knockdown cells. Epithelial-mesenchymal transition (EMT) was regulated by miR-223-3p. In addition, cell apoptosis was suppressed and enhanced by miR-223-3p over-expression and knockdown, respectively. We further identified PRDM1, a tumor suppressor, was the target of miR-223-3p using microarray and luciferase assay. Our findings suggested that miR-223-3p acts as an oncogenic microRNA in colon cancer through regulating EMT and PRDM1.