Long non-coding RNA BX357664 inhibits gastric cancer progression by sponging miR-183a-3p to regulate the PTEN expression and PI3K/AKT pathway.

Lately, long non-coding RNA (lncRNA) is recognized as a key regulator of gastric cancer (GC) which has aroused great interest in the fields of medicine, toxicology, and functional food. Studies related to LncRNA expression microarray data indicate that BX357664 is down-regulated in GC specimens. However, the expression pattern and molecular mechanism of BX357664 in GC have not been studied so far. The purpose of this study was to investigate the expression of lncRNA BX357664 in GC and its function in GC cell lines. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of BX357664 in 50 pairs of cancer tissues and adjacent non-cancer tissues collected from GC patients. It was found that BX357664 level was lowered in cancer specimens than adjacent non-cancer tissues and correlated with tumor size and TNM stage. Also, we used cell counting kit 8 (CCK8), cell clone formation assay and transwell assay, which affirmed that up-regulation of BX357664 inhibited the proliferation, migration, and invasion of GC cells, but promoted apoptosis. In the dual-luciferase report analysis, BX357664 acted as a miR-183-3p ceRNA to target and regulate the expression of PTEN and affect the PI3K/AKT pathway. These results indicate that BX357664 can inhibit the proliferation and metastasis of GC through the miR-183-3p/PTEN/PI3K/AKT pathway, which may serve as potential targets for the treatment of GC in the future.

G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner.

Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.

Helicobacter pylori CagA induces tumor suppressor gene hypermethylation by upregulating DNMT1 via AKT-NFκB pathway in gastric cancer development.

Methylation of CpG islands in tumor suppressor gene prompter is one of the most characteristic abnormalities in Helicobacter pylori (HP)-associated gastric carcinoma (GC). Here, we investigated the pathogenic and molecular mechanisms underlying hypermethylation of tumor suppressor genes in HP induced GC development. We found that tumor suppressor genes hypermethylation, represented by MGMT, positively correlated with CagA in clinical specimens, gastric tissues from HP infected C57 mice and GC cell lines transfected by CagA or treated by HP infection. CagA enhanced PDK1 and AKT interaction and increased AKT phosphorylation. The P-AKT subsequent activated NFκB, which then bound to DNMT1 promoter and increased its expression. Finally, the upregulated DNMT1 promoted tumor suppressor genes hypermethylation with MGMT as a representative. In conclusion, CagA increased tumor suppressor genes hypermethylation via stimulating DNMT1 expression through the AKT-NFκB pathway.

Spatial Variations of Soil Microbial Activities in Saline Groundwater-Irrigated Soil Ecosystem.

Spatial variations of soil microbial activities and its relationship with environmental factors are very important for estimating regional soil ecosystem function. Based on field samplings in a typical saline groundwater-irrigated region, spatial variations of soil microbial metabolic activities were investigated. Combined with groundwater quality analysis, the relationship between microbial activities and water salinity was also studied. The results demonstrated that moderate spatial heterogeneity of soil microbial activities presented under the total dissolved solids (TDS) of groundwater ranging from 0.23 to 12.24 g L(-1). Groundwater salinity and microbial activities had almost opposite distribution characteristics: slight saline water was mainly distributed in west Baqu and south Quanshan, while severe saline and briny water were dominant in east Baqu and west Huqu; however, total AWCD was higher in the east-center and southwest of Baqu and east Huqu, while it was lower in east Baqu and northwest Huqu. The results of correlation analyses demonstrated that high-salinity groundwater irrigation had significantly adverse effects on soil microbial activities. Major ions Ca(2+), Mg(2+), Cl(-), and SO4(2-) in groundwater decisively influenced the results. Three carbon sources, carbohydrates, amines, and phenols, which had minor utilization rates in all irrigation districts, were extremely significantly affected by high-salinity groundwater irrigation. The results presented here offer an approach for diagnosing regional soil ecosystem function changes under saline water irrigation.

Androgen receptor promotes gastric cancer cell migration and invasion via AKT-phosphorylation dependent upregulation of matrix metalloproteinase 9.

Androgen receptor (AR) plays an important role in many kinds of cancers. However, the molecular mechanisms of AR in gastric cancer (GC) are poorly characterized. Here, we investigated the role of AR in GC cell migration, invasion and metastatic potential. Our data showed that AR expression was positively correlated with lymph node metastasis and late TNM stages. These findings were accompanied by activation of AKT and upregulation of matrix metalloproteinase 9 (MMP9). AR overexpression induced increases in GC cell migration, invasion and proliferation in vitro and in vivo. These effects were attenuated by inhibition of AKT, AR and MMP9. AR overexpression upregulated MMP9 protein levels, whereas this effect was counteracted by AR siRNA. Inhibition of AKT by siRNA or an inhibitor (MK-2206 2HC) decreased AR protein expression in both stably transfected and parental SGC-7901 cells. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that AR bound to the AR-binding sites of the MMP9 promoter. In summary, AR overexpression induced by AKT phosphorylation upregulated MMP9 by binding to its promoter region to promote gastric carcinogenesis. The AKT/AR/MMP9 pathway plays an important role in GC metastasis and may be a novel therapeutic target for GC treatment.

microRNA-21 promotes tumor proliferation and invasion in gastric cancer by targeting PTEN.

Gastric cancer is one of the most common carcinomas in China. microRNAs, a type of non-coding RNA, are important specific regulators and are involved in numerous bioprocesses of an organism. microRNA-21 (miR-21) has been identified as the most suitable choice for further investigation because it is overexpressed in nearly all solid tumors; furthermore, it has been demonstrated that miR-21 is involved in the genesis and progression of human cancer. It has been reported that PTEN, an important tumour suppressor, is regulated by multiple miRNAs. Thus, in this study we focused on the expression and significance of miR-21 in gastric cancer tissues, and the role of miR-21 in the biological behaviour and the expression of PTEN in gastric cancer cells. Real-time PCR was used to detect miR-21 expression in gastric cancer tissues, the adjacent normal tissues, and the gastric cell lines. The gastric cancer cell line BGC-823 was transfected with pre-miR-21/miR-21 inhibitor to overexpress/downregulate miR-21. The influence of miR-21 on the biological behaviour of gastric cancer cells was evaluated using the CCK-8 kit, FCMs, the scratch healing assay and the transwell test. Western blotting and the Luciferase Reporter Assay were used to evaluate the change of PTEN expression after lowered expression of miR-21 in gastric cancer cell lines. Real-time PCR analysis indicated that miR-21 exhibited higher expression in gastric cancer tissues compared to the adjacent non-tumor tissues. miR-21 expression was significantly associated with the degree of differentiation of the tumour tissues (P=0.004), as well as local invasion and lymph node metastasis (P<0.01). After transfection, pre-miR21 BGC-823 cells grew faster than the negative and control groups (P<0.01). The reduction in miR-21 expression demonstrated a remarkable effect on the biological behaviour of gastric cancer cells (P<0.05); the pre-miR-21-transfected cells healed more quickly compared to the control cells in the scratch healing assay, whereas the transwell test indicated that cell migration in vitro was notably inhibited with the downregulation of miR-21 (P<0.05). The western blot results and Luciferase Reporter Assay demonstrated that PTEN expression was remarkably increased after miR-21 inhibition (P<0.05). microRNA-21 expression was upregulated in gastric carcinoma tissues and was significantly associated with the degree of differentiation of tumour tissues, local invasion and lymph node metastasis. Overexpression of miR-21 promoted BGC-823 cell growth, invasion and cell migration in vitro, whereas downregulation of miR-21 exhibited a stronger inhibitory effect on the biological behaviour of gastric cancer cells; additionally, miR-21 inhibition may upregulate the PTEN expression level, which indicates that PTEN may be a target gene for gastric cancer initiation and development.

Three-dimensional distribution of vessels, passage cells and lateral roots along the root axis of winter wheat (Triticum aestivum).

BACKGROUND AND AIMS: The capacity of a plant to absorb and transport water and nutrients depends on anatomical structures within the roots and their co-ordination. However, most descriptions of root anatomical structure are limited to 2-D cross-sections, providing little information on 3-D spatial relationships and hardly anything on their temporal evolution. Three-dimensional reconstruction and visualization of root anatomical structures can illustrate spatial co-ordination among cells and tissues and provide new insights and understanding of the interrelation between structure and function. METHODS: Classical paraffin serial-section methods, image processing, computer-aided 3-D reconstruction and 3-D visualization techniques were combined to analyse spatial relationships among metaxylem vessels, passage cells and lateral roots in nodal roots of winter wheat (Triticum aestivum). KEY RESULTS: 3-D reconstruction demonstrated that metaxylem vessels were neither parallel, nor did they run directly along the root axis from the root base to the root tip; rather they underwent substitution and transition. Most vessels were connected to pre-existent or newly formed vessels by pits on their lateral walls. The spatial distributions of both passage cells and lateral roots exhibited similar position-dependent patterns. In the transverse plane, the passage cells occurred opposite the poles of the protoxylem and the lateral roots opposite those of the protophloem. Along the axis of a young root segment, the passage cells were arranged in short and discontinuous longitudinal files, thus as the tissues mature, the sequence in which the passage cells lose their transport function is not basipetal. In older segments, passage cells decreased drastically in number and coexisted with lateral roots. The spatial distribution of lateral roots was similar to that of the passage cells, mirroring their similar functions as lateral pathways for water and nutrient transport to the stele. CONCLUSIONS: With the 3-D reconstruction and visualization techniques developed here, the spatial relationships between vessels, passage cells and lateral roots and the temporal evolution of these relationships can be described. The technique helps to illustrate synchronization and spatial co-ordination among the root's radial and axial pathways for water and nutrient transport and the interdependence of structure and function in the root.