The Activated Notch1 Signal Pathway Is Associated with Gastric Cancer Progression through Cyclooxygenase-2

Gastric carcinoma is one of the most common cancers and lethal malignancies worldwide. Thus far, the regulatory mechanisms of its aggressiveness are still poorly understood . To understand the pathogenesis and to develop new therapeutic strategies, it is essential to dissect the molecular mechanisms that regulate progression of gastric cancer. Herein, we sought to address whether Notch1 signal pathway is involved in the control of progression in gastric cancer. We found that expression of Notch ligand Jagged1 was correlated with aggressiveness of human gastric cancer. Patients with Jagged1 expression in gastric cancer tissues had a poor survival rate compared with those without Jagged1 expression. The Notch1 receptor intracellular domain (N1IC) , the activated form of Notch1 receptor, promoted the colony -forming ability and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. Migration and invasion abilities of SC-M1 cells were enhanced by N1IC. Furthermore, N1IC and C promoter-binding factor 1 (CBF1) bound to cyclooxygenase-2 (COX-2) promoter and elevated COX-2 expression in SC-M1 cells through a CBF1-dependent manner. The colony-forming, migration, and invasion abilities enhanced by N1IC were suppressed in SC-M1 cells after treatment with the COX-2 inhibitor NS-398 or knockdown of COX-2. These cellular processes inhibited by Notch1 knockdown were restored by prostaglandin E-2 or exogenous COX-2. Taken together, these results suggest that activation of Notch1 signal pathway promotes progression of gastric cancer, at least in part through COX-2

Link between Crustal Magnetization and Earthquakes in Taiwan

The active Taiwan orogen is located between the Ryukyu subduction zone in the northeast and the Manila subduction zone in the south. Intensive collision from the northwestward motion of the Luzon Arc has induced enormous earthquakes in and around Taiwan. In this paper, we attempt to relate the occurrence of earthquakes in Taiwan to crustal magnetization. For that, we have inverted magnetic anomalies to obtain an equivalent crustal magnetization distribution in the Taiwan region. In general, high magnetization zones are considered as relatively rigid zones. In contrast, weak zones can be compressed as a result of lateral plate convergence, causing intensively crustal deformation and earthquakes. The Lukang Magnetization High (LMH), located in mid-west Taiwan, is suggested to dominate earthquake occurrence in middle Taiwan. Historically large earthquakes in Taiwan are mostly distributed around the eastern side of the LMH. If we take into account the northwestward convergence of the Luzon Arc or the Philippine Sea Plate, the area to the southeastern side of the LMH actually incubates more earthquake hazards. The crust of relatively low magnetization in mid-central Taiwan has been compressed and escaped sideward; intensive compression has also caused thicker crust and the depths of crustal earthquakes in middle Taiwan may be as deep as 40 km. Although both the eastern Central Range and the Luzon Arc show relatively high magnetizations, the Luzon Arc may be intrinsically less stable because of its younger and hotter nature; thus, the Luzon Arc has historically displayed severe internal deformation and produced numerous earthquakes as a result of plate collision

miR-151-3p Targets TWIST1 to Repress Migration of Human Breast Cancer Cells.

TWIST1 is a highly conserved basic helix-loop-helix transcription factor that contributes to cancer metastasis by promoting an epithelial-mesenchymal transition and repressing E-cadherin gene expression in breast cancer. In this study, we explored the potential role of miR-151 in TWIST1 expression and cancer properties in human breast cancer cells. We found that the human TWIST1 3'UTR contains a potential binging site for miR-151-3p at the putative target sequence 5'-CAGUCUAG-3'. Using a TWIST1-3'UTR luciferase reporter assay, we demonstrated that the target sequence within the TWIST1 3'UTR is required for miR-151-3p regulation of TWIST1 expression. Moreover, we found that ectopic expression of miR-151-3p by infection with adenoviruses expressing miR-151 significantly decreased TWIST1 expression, migration and invasion, but did not affect cell growth and tumorsphere formation of human breast cancer cells. In addition, overexpression of the protein coding region without the 3'UTR of TWIST1 reversed the repression of cell migration by miR-151-3p. Furthermore, knockdown of miR-151-3p increased TWIST1 expression, reduced E-cadherin expression, and enhanced cell migration. In conclusion, these results suggest that miR-151-3p directly regulates TWIST1 expression by targeting the TWIST1 3'UTR and thus repressing the migration and invasion of human breast cancer cells by enhancing E-cadherin expression. Our findings add to accumulating evidence that microRNAs are involved in breast cancer progression by modulating TWIST1 expression

Yin Yang 1 is a target of microRNA-34 family and contributes to gastric carcinogenesis.

Gastric cancer is the second leading cause of cancer-related death worldwide. Herein, we investigated the role of transcription factor Yin Yang 1 (YY1), a multi-functional protein, in tumorigenesis of gastric cancer cells. Results showed that YY1 contributed to gastric carcinogenesis of SC-M1 cells including growth, viability, and abilities of colony formation, migration, invasion, and tumorsphere formation. Levels of pluripotency genes CD44, Oct4, SOX-2, and Nanog were also up-regulated by YY1 in SC-M1 cells. Additionally, the 3'-untranslated region (3'-UTR) of YY1 mRNA was the target of microRNA-34 (miR-34) family consisting of miR-34a, miR-34b, and miR-34c. Overexpression of miR-34 family suppressed carcinogenesis through down-regulation of YY1 in NUGC-3 gastric cancer cells scarcely expressing miR-34 family. Alternatively, knockdown of miR-34 family promoted tumorigenesis via up-regulation of YY1 in SC-M1 and AZ521 gastric cancer cells with higher levels of miR-34 family. The miR-34 family also affected tumorsphere ultra-structure and inhibited the xenografted tumor growth as well as lung metastasis of SC-M1 cells through YY1. Expressions of miR-34a and miR-34c in gastric cancer tissues of patients were lower than those in normal tissues. Taken together, these results suggest that miR-34 family-YY1 axis plays an important role in the control of gastric carcinogenesis