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Background The small GTPase Ran is upregulated in multiple cancers and fundamental for cancer cell survival and progression, but its significance and molecular mechanisms in colorectal cancer (CRC) remain elusive. Methods Ran expression was detected in CRC cell lines and tumour tissues. In vitro and in vivo functional assays were performed to examine the effects of Ran on cell proliferation and metastasis. The pathways and effectors regulated by Ran were explored by an unbiased screening. Bioinformatics prediction and experimental validation were used to identify the miRNA regulator for Ran. Results Ran expression was frequently increased in metastatic CRC cells and tissues, especially in metastatic tissues. The upregulation of Ran correlated with poor CRC patient prognosis. Ran silencing reduced proliferation and metastasis of CRC cells both in vitro and in vivo. Ran regulated the expression of EGFR and activation of ERK and AKT signalling pathways. miR-802 was identified as an upstream regulator of Ran and miR-802 overexpression resulted in antiproliferative and antimetastatic activities. Conclusion Our study demonstrates the oncogenic roles and underlying mechanisms of Ran in CRC and the novel miR-802/Ran/EGFR regulatory axis may provide potential biomarkers for the treatment of CRC.

Aberrant activation of the Wnt/β-catenin signaling pathway is implicated in most malignant cancers, especially in the initiation and progression of colorectal cancer (CRC). DKK4 is a classical inhibitory molecule of the Wnt/β-catenin pathway, but its role in CRC is ambiguous, and the molecular mechanism remains unclear. Here, we determined DKK4 expression was significantly upregulated in 23 CRC cell lines and 229 CRC tissues when analyzed by quantitative PCR and immunohistochemistry, respectively. Our analysis of tissue samples indicated the survival time of CRC patients with high DKK4 expression was longer than that of patients with medium-low DKK4 expression. We examined the effects of DKK4 on cell proliferation and metastasis by cell counting kit-8 assays, transwell assays, and subcutaneous and metastatic mouse tumor models, and we discovered that DKK4 silencing promoted the metastasis of CRC cells both in vitro and in vivo. Our RNA-seq analysis revealed that AKT2, FZD6, and JUN, which play important roles in AKT and Wnt signaling, were significantly increased after DKK4 knockdown. DKK4 represses Wnt/β-catenin signaling by repressing FZD6 and AKT2/s552 β-catenin in CRC. Further experiments revealed recombinant Wnt3a and LiCl could induce DKK4 expression. Moreover, our bioinformatics analysis and luciferase reporter assays identified posttranscriptional regulators of DKK4 in CRC cells. In summary, DKK4 is elevated in CRC and inhibits cell metastasis by a novel negative feedback mechanism of the Wnt3a/DKK4/AKT/s552 β-catenin regulatory axis to restrict overactivation of Wnt activity in CRC. Therefore, DKK4 restoration may be applied as a potential CRC therapeutic strategy.

Acer truncatum seed coat is generally abandoned as waste during the process of manufacturing seed oil due to a lack of knowledge of the phytochemical composition of this byproduct. It is well known that brown-colored seed coat is rich in polyphenols; therefore, we investigated the bioactive phenolic composition of A. truncatum seed coat in this study. To obtain an extract containing most bioactive phenolic compounds, extractions in six solutions (water, 40% ethanol, 70% ethanol, 100% ethanol, 70% acetone, and 100% acetone) were compared for their yields, phenolic contents, and antioxidant activities. The 70% ethanol extract, which had the highest yield at 76.38 g extract/100 g dry matter, showed the highest levels of total phenols, total flavonoids, total tannins, and condensed tannins, as well as the highest DPPH and ABTS+ scavenging activities. UPLC-QTOF-MS analyses resulted in identification of 13 phenolic compounds in the 70% ethanol extract, among which five compounds, gentisic acid, naringenin, epicatechin, procyanidin tetramer, and procyanidin pentamer, were identified for the first time in A. truncatum. Five flavonoids and four procyanidin oligomers were the dominant phenolic components, comprising 63.27% and 31.02% of the 13 phenolic compounds, respectively. Correlation analyses revealed that flavonoids and tannins were the major factors responsible for the high antioxidant activities, suggesting that these two components of A. truncatum seed coat could be developed as alternative antioxidants. This is the first known report on the phenolic composition of seed coats in the genus Acer.

The sequential growth of winter wheat and corn within one year is the main cropping rotation system in northern China, excess nitrogen (N) fertilizer application to this system is a common problem. Four field experiments with four or five N rates were conducted in Beijing City and Henan province to study the optimal N rate for this system. The results of this study clearly indicate that the high rates of fertilization recommended by the quadratic model were less profitable than the lower rates recommended by the LRP and QRP models. The amounts of N in above-ground plant tissue tended to increase with increase in rate of N application but the percentage recovery of N in each increment decreased with each additional increment of fertilizer applied, and higher percentage recoveries were observed in wheat than in corn. Soil nitrate concentrations increased with increasing rates of N application. Average of 30% of the soil mineral N deficit can be accounted for uptake of N by wheat, but linear regress...