Phase separation of RNF214 promotes the progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

Circ_0003789 Facilitates Gastric Cancer Progression by Inducing the Epithelial-Mesenchymal Transition Through the Wnt/ß-Catenin Signaling Pathway.

Background: The role of circular RNAs in the pathogenesis of gastric cancer (GC) has been well documented by numerous studies. However, whether circ_0003789 plays a role during GC progression remains to be determined. Thus, this study investigated the biological functions of circ_0003789 during GC progression. Materials and Methods: Circ_0003789 expression was determined using quantitative real-time polymerase chain reaction in GC and matched para-carcinoma normal tissues. Functional experiments were performed to estimate changes in the proliferation, apoptosis, migration, and invasion of GC cells treated to silence circ_0003789. E-cadherin, vimentin, Wnt3a, and ß-catenin expression was determined using immunofluorescence staining and Western blot assays. Xenograft tumor growth and Ki67 expression were also evaluated in vivo. Results: Circ_0003789 was upregulated in GC tissues and cells, and its upregulation positively correlated with poor tumor differentiation, distal metastasis, and advanced clinical stage. Silencing circ_0003789 inhibited GC cell proliferation, migration, invasion, and the epithelial-mesenchymal transition (EMT), both in vitro and in vivo. Mechanistically, the Wnt/ß-catenin signaling pathway was repressed by circ_0003789 silencing. Conclusions: Circ_0003789 facilitates GC progression by inducing the EMT through the Wnt/ß-catenin signaling pathway.

The NOTCH-HES-1 axis is involved in promoting Th22 cell differentiation.

BACKGROUND: NOTCH signaling has been shown to play a role in the production of interleukin-22 (IL-22) by CD4+ T cells. Multiple T-helper (Th) cell populations secrete IL-22. Th22 (CD4+IL22+IFNγ-IL17A-) cells are a subgroup of CD4+ effector T cells that primarily generate IL-22. The regulatory mechanisms of the NOTCH signaling pathway involved in differentiation of the Th22 cell subset have not been completely elucidated. This study aimed to further explore the involvement of NOTCH signaling in Th22 differentiation. METHODS: In vitro combination of IL-6, IL-23, and tumor necrosis factor-α (TNF-α) treatment with naïve CD4+ T cells established the Th22 cell induced model. NOTCH signaling was activated by jagged-1 and inhibited by (2S)-N-[(3,5-difluorophenyl) acetyl]-L-alanyl-2-phenyl]glycine 1,1-dimethylethyl ester (DAPT). HES-1 siRNA and HES-1 vector were employed to knock down and induce overexpression of HES-1 to investigate the effect of NOTCH signaling on the differentiation of CD4+T cells into Th22 cells. RESULTS: We observed that the proportion of Th22 cells, along with Hes-1, Ahr, and Il-22 mRNA and protein expression, was increased by both jagged-1 and overexpression of HES-1. On the other hand, after the combined cytokine treatment of cells, and exposure to jagged-1 and DAPT or HES-1 siRNA, there was a decrease in the Th22 cell proportion, mRNA and protein expression of HES-1, AHR, and IL-22. CONCLUSIONS: Our study demonstrates that HES-1 enhancement in AHR and IL-22 up-regulation of NOTCH signaling can promote the skewing of naïve CD4+T cells toward Th22 cells. Also, the results of our study show that HES-1 is a crucial factor in Th22 cell differentiation.

An improved method used for evaluating potential environmental pollution risk based on spatial distribution and density of farms.

The livestock manure nitrogen load on farmland (LMNLF) is often used to assess the potential environmental pollution risk of livestock manure nitrogen nutrient (LMN) in a target region. First, the LMNLF of Wuhan city is calculated, and the potential environmental pollution risk of LMN is mainly concentrated in Jiangxia District, Xinzhou District, and Huangpi District, but does not exceed the European Union (EU) standards. Heat map results also certificate this conclusion. Therefore, these three districts are the research emphases. Second, considering spatial distribution of farms, an improved LMNLF method is proposed combining the previous LMNLF and density-based spatial clustering of applications with noise (DBSCAN) methods. Several regions with pollution risks including seven regions in Jiangxia District, one in Xinzhou District, and one in Huangpi District are found out using the improved LMNLF method. Third, to evaluate the carrying capacity of the intensive breeding areas more reasonably, 2 km is taken as the farthest transportation distance of manure; there is still one region in Huangpi District which has serious pollution risk on the environment. These above results can help evaluate the pollution degree of livestock manure to the surrounding environment more precisely.