NF-κB interacting lncRNA (NKILA) has been found to function as a tumor-suppressive role in various human cancers. However, the role of NKILA in rectal cancer is still unknown. The objective of this study is to investigate the clinical value and biological function of NKILA in rectal cancer. The association between NKILA expression and clinical variables including prognosis was estimated in rectal cancer patients. The gain-of-function study of NKILA in rectal cancer cell was conducted to evaluate the effect of NKILA on cell proliferation, migration, invasion, and NF-κB signaling pathway. The results suggested NKILA expression was decreased in rectal cancer tissues and cells, and correlated with clinical stage, T classification, N classification and M classification. NKILA low-expression was an independent poor prognostic factor in rectal cancer patients. NKILA-inhibited rectal cancer cell proliferation, migration, and invasion via suppressing NF-κB signaling. In conclusion, NKILA serves as an antioncogenic lncRNA in rectal cancer.

No abstract

Amentoflavone (AF) is a natural multifunctional biflavonoid that has been revealed to possess multiple biological activities, including anticancer activity. Here, this work focused on exploring the functions and mechanism of AF in gastric cancer (GC). Levels of genes and proteins were examined by quantitative real‐time PCR and western blotting. Cell proliferation and cell death were analyzed using cell counting kit‐8, colony formation, and lactate dehydrogenase (LDH) release assay, respectively. Cell ferroptosis was evaluated by detecting the levels of malondialdehyde (MDA), reduced glutathione (GSH), Fe2+, and intracellular reactive oxygen species (ROS). The binding between miR‐496 and activating transcription factor 2 (ATF2) was confirmed by using dual‐luciferase reporter assay. Murine xenograft assay was conducted for in vivo experiments. The results showed that AF suppressed the proliferation and induced ferroptotic cell death in GC cells. MiR‐496 expression was decreased in GC tissues and cells, and AF treatment increased miR‐496 expression level in GC cells. Functionally, miR‐496 inhibition reversed the inhibitory effects of AF on GC cell proliferation and promoting effects on ferroptotic cell death. Mechanistically, ATF2 was targeted by miR‐496. ATF2 expression was increased in GC tissues and cells, which was decreased by AF treatment and subsequently rescued by miR‐496 downregulation in GC cells. Moreover, miR‐496 overexpression suppressed the proliferation and induced ferroptotic cell death in GC cells via targeting ATF2. In all, AF suppressed the proliferation and induced ferroptotic cell death in GC cells via miR‐496/ATF2 axis, indicating a novel therapeutic approach for GC patients.

Food digestion requires the cooperation of different digestive organs. The differentiation of digestive organs is crucial for larvae to start feeding. Therefore, during digestive organogenesis, cell identity and the tissue morphogenesis must be tightly coordinated but how this is accomplished is poorly understood. Here, we demonstrate that WD repeat domain 5 (Wdr5)-mediated H3K4 tri-methylation (H3K4me3) coordinately regulates cell differentiation, proliferation and apoptosis in zebrafish organogenesis of three major digestive organs including intestine, liver, and exocrine pancreas. During zebrafish digestive organogenesis, some of cells in these organ primordia usually undergo differentiation without apoptotic activity and gradually reduce their proliferation capacity. In contrast, cells in the three digestive organs of wdr5−/− mutant embryos retain progenitor-like status with high proliferation rates, and undergo apoptosis. Wdr5 is a core member of COMPASS complex to implement H3K4me3 and its expression is enriched in digestive organs from 2 days post-fertilization (dpf). Further analysis reveals that lack of differentiation gene expression is due to significant decreases of H3K4me3 around the transcriptional start sites of these genes; this histone modification also reduces the proliferation capacity in differentiated cells by increasing the expression of apc to promote the degradation of β-Catenin; in addition, H3K4me3 promotes the expression of anti-apoptotic genes such as xiap-like, which modulates p53 activity to guarantee differentiated cell survival. Thus, our findings have discovered a common molecular mechanism for cell fate determination in different digestive organs during organogenesis, and also provided insights to understand mechanistic basis of human diseases in these digestive organs.