Cancer associated fibroblasts-derived SULF1 promotes gastric cancer metastasis and CDDP resistance through the TGFBR3-mediated TGF-ß signaling pathway.

SULF1 has been implicated in a number of malignancies. The function of SULF1 in gastric cancer is disputed. The objective of this study was to examine the role and underlying molecular mechanisms of SULF1 in the context of gastric cancer. We found that the expression of SULF1 was increased in gastric cancer, especially in cancer-associated fibroblasts. The overexpression of SULF1 was found to be significantly correlated with unfavorable prognosis among individuals diagnosed with gastric cancer. Functionally, cancer-associated fibroblasts-derived SULF1 served as a oncogenic molecule which facilitated gastric cancer cells metastasis and CDDP resistance. Mechanistically, SULF1 regulated the communication between gastric cancer cells and cancer-associated fibroblasts in tumor microenvironment as a signaling molecule. Cancer-associated fibroblasts-secreted SULF1 interfered with the interaction between TGF-ß1 and TGFBR3 by combining with TGFBR3 on gastric cancer cell membrane, subsequently activated TGF-ß signaling pathway. In conclusion, our findings have presented novel approaches for potential treatment and prognosis prediction in individuals diagnosed with gastric cancer through the targeting of the CAFs-SULF1-TGFBR3-TGF-ß1 signaling axis.

N6-methyladenosine-modified MIB1 promotes stemness properties and peritoneal metastasis of gastric cancer cells by ubiquitinating DDX3X.

BACKGROUND: Peritoneal metastasis (PM), one of the most typical forms of metastasis in advanced gastric cancer (GC), indicates a poor prognosis. Exploring the potential molecular mechanism of PM is urgently necessary, as it has not been well studied. E3 ubiquitin ligase has been widely established to exert a biological function in various cancers, but its mechanism of action in GC with PM remains unknown. METHODS: The effect of MIB1 on PM of GC was confirmed in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrometry demonstrated the association between MIB1 and DDX3X. Western blot, flow cytometry and immunofluorescence determined that DDX3X was ubiquitylated by MIB1 and promoted stemness. We further confirmed that METTL3 promoted the up-regulation of MIB1 by RNA immunoprecipitation (RIP), luciferase reporter assay and other experiments. RESULTS: We observed that the E3 ubiquitin ligase Mind bomb 1 (MIB1) was highly expressed in PMs, and patients with PM with high MIB1 expression showed a worse prognosis than those with low MIB1 expression. Mechanistically, our study demonstrated that the E3 ubiquitin ligase MIB1 promoted epithelial-mesenchymal transition (EMT) progression and stemness in GC cells by degrading DDX3X. In addition, METTL3 mediated m6A modification to stabilize MIB1, which required the m6A reader IGF2BP2. CONCLUSIONS: Our study elucidated the specific molecular mechanism by which MIB1 promotes PM of GC, and suggested that targeting the METTL3-MIB1-DDX3X axis may be a promising therapeutic strategy for GC with PM.

ACLY promotes gastric tumorigenesis and accelerates peritoneal metastasis of gastric cancer regulated by HIF-1A.

Mounting evidence indicates the potential involvement of ATP-citrate lyase (ACLY) in the modulation of various cancer types. Nevertheless, the precise biological significance of ACLY in gastric cancer (GC) remains elusive. This study sought to elucidate the biological function of ACLY and uncover its influence on peritoneal metastasis in GC. The expression of ACLY was assessed using both real-time quantitative PCR and western blot techniques. To investigate the impact of ACLY on the proliferation of gastric cancer (GC) cells, colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed. The migratory and invasive abilities of GC were evaluated using wound healing and transwell assays. Additionally, a bioinformatics analysis was employed to predict the correlation between ACLY and HIF-1A. This interaction was subsequently confirmed through a chromatin immunoprecipitation (ChIP) assay. ACLY exhibited upregulation in gastric cancer (GC) as well as in peritoneal metastasis. Its overexpression was found to facilitate the proliferation and metastasis of GC cells in both in vitro and in vivo experiments. Moreover, ACLY was observed to play a role in promoting angiogenesis and epithelial-mesenchymal transition (EMT). Notably, under hypoxic conditions, HIF-1A levels were elevated, thereby acting as a transcription factor to upregulate ACLY expression. Under the regulatory influence of HIF-1A, ACLY exerts a significant impact on the progression of gastric cancer, thereby facilitating peritoneal metastasis.

Peritoneal high-fat environment promotes peritoneal metastasis of gastric cancer cells through activation of NSUN2-mediated ORAI2 m5C modification.

Peritoneal metastasis (PM) is an important metastatic modality of gastric cancer (GC).It is associated with poor prognosis. The underlying molecular mechanism of PM remains elusive. 5-Methylcytosine (m5C), a posttranscriptional RNA modification, involves in the progression of many tumors. However, its role in GC peritoneal metastasis remains unclear. In our study, transcriptome results suggested that NSUN2 expression was significantly upregulated in PM. And patients with high NSUN2 expression of PM predicted a worse prognosis. Mechanistically, NSUN2 regulates ORAI2 mRNA stability by m5C modification, thereby promoting ORAI2 expression and further promoting peritoneal metastasis and colonization of GC. YBX1 acts as a "reader" by binding to the ORAI2 m5C modification site. Following the uptake of fatty acids from omental adipocytes by GC cells, the transcription factor E2F1 was upregulated, which further promoted the expression of NSUN2 through cis-element. Briefly, these results revealed that peritoneal adipocytes provide fatty acid for GC cells, thus contributing to the elevation of E2F1 and NSUN2 through AMPK pathway, and upregulated NSUN2 activates the key gene ORAI2 through m5C modification, thereby promoting peritoneal metastasis and colonization of gastric cancer.

Detecting Wheat Powdery Mildew and Predicting Grain Yield Using Unmanned Aerial Photography.

High-resolution aerial imaging with an unmanned aerial vehicle (UAV) was used to quantify wheat powdery mildew and estimate grain yield. Aerial digital images were acquired at Feekes growth stage (GS) 10.5.4 from flight altitudes of 200, 300, and 400 m during the 2009-10 and 2010-11 seasons; and 50, 100, 200, and 300 m during the 2011-12, 2012-13, and 2013-14 seasons. The image parameter lgR was consistently correlated positively with wheat powdery mildew severity and negatively with wheat grain yield for all combinations of flight altitude and year. Fitting the data with random coefficient regression models showed that the exact relationship of lgR with disease severity and grain yield varied considerably from year to year and to a lesser extent with flight altitude within the same year. The present results raise an important question about the consistency of using remote imaging information to estimate disease severity and grain yield. Further research is needed to understand the nature of interyear variability in the relationship of remote imaging data with disease or grain yield. Only then can we determine how the remote imaging tool can be used in commercial agriculture.