The lncRNA-MALAT1/miR-330-3p Axis Promotes Growth and Metastasis of Gastric Cancer Through Regulation of Vascular Endothelial Growth Factor A: A Genetic and Cell Evaluation Study

SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.

Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.

LncRNA SND1-IT1 facilitates TGF-ß1-induced epithelial-to-mesenchymal transition via miR-124/COL4A1 axis in gastric cancer.

The transformation of tumor cells from an epithelial to a mesenchymal-like phenotype, designated as epithelial-to-mesenchymal transition (EMT), represents a key hallmark of human cancer metastasis, including gastric cancer (GC). However, a large set of non-coding RNAs have been studied for their functions that initiate or inhibit this phenotypic switch in GC cells by regulating oncogenes or tumor suppressors. In this paper, we aimed to identify lncRNA SND1-IT1, miR-124, and COL4A1 gene in the context of GC with a specific focus on their effects on transforming growth factor ß1 (TGF-ß1)-induced EMT. The study included 52 paired samples of lesion tissues and adjacent lesion-free tissues surgically resected from patients diagnosed with GC. HGC-27 cells were stimulated with exogenous TGF-ß1 (2 ng/mL). Expression of lncRNA SND1-IT1, miR-124, and COL4A1 was determined by RT-qPCR. CCK-8 assays, Transwell assays, immunoblotting analysis of EMT-specific markers, and tumor invasion markers were performed to evaluate cell viability, migration, and invasion of cultured HGC-27 cells. Luciferase activity assay was employed to examine miR-124 binding with lncRNA SND1-IT1 and COL4A1, respectively. LncRNA SND1-IT1 was upregulated in GC tissues and cells. TGF-ß1-stimulated EMT and regulated lncRNA SND1-IT1, miR-124, and COL4A1 expressions in HGC-27 cells. LncRNA SND1-IT1 knockdown tempered HGC-27 cell viability, migration and invasion. LncRNA SND1-IT1 participated in TGF-ß1-stimulated EMT in GC by sponging miR-124. MiR-124 attenuated TGF-ß1-stimulated EMT in GC by targeting COL4A1. These results primarily demonstrated TGF-ß1 can regulate cancer cell migration, invasion and stimulate EMT through the SND1-IT1/miR-124/COL4A1 axis in GC.

The overexpression of ZWINT in integrated bioinformatics analysis forecasts poor prognosis in breast cancer.

BACKGROUND: Zeste White 10 interactor (ZW10 interactor, ZWINT) is a centromeric complex required for a mitotic spindle checkpoint. According to previous studies, it was overexpressed in people with recurrent tumors. However, the expression of ZWINT in breast cancer has not been thoroughly studied. In addition, the correlations of ZWINT to prognosis in breast cancer remain unclear. METHODS: In this study, the expression of ZWINT in different types of tumors was analyzed based on the Oncomine database, and the effect of ZWINT expression on clinical prognosis was evaluated by Kaplan-Meier plotter. RESULTS: In breast cancer, lung cancer, sarcoma, ovarian cancer, bladder cancer, liver cancer and cervical cancer, the expression of ZWINT was higher than that in normal tissues, but in gastric cancer, prostate cancer, myeloma, renal cancer and pancreatic cancer, the expression of ZWINT was lower. In addition, a meta-analysis of 22 cancer database studies found that the ZWINT gene was over-expressed in breast cancer tissues compared with normal tissues (P=4.05×10-6). Through the survival analysis of Kaplan-Meier plotter, it is found that the high expression of ZWINT is related to the worse overall survival (OS) [hazard ratio (HR) =1.73, 95% confidence interval (CI): 1.39-2.51, P=5.4×10-7], RFS (HR =1.68, 95% CI: 1.51-1.88, P<1×10-16) and distant metastasis-free survival (DMFS) (HR =1.55, 95% CI: 1.28-1.89, P=7.9×10-6) in all BC patients. CONCLUSIONS: Our results strongly suggest that over expression of ZWINT is closely related to poor prognosis of breast cancer. ZWINT may be a prognostic biomarker for the treatment of BC.

Metallic resist for phase-change lithography.

Currently, the most widely used photoresists in optical lithography are organic-based resists. The major limitations of such resists include the photon accumulation severely affects the quality of photolithography patterns and the size of the pattern is constrained by the diffraction limit. Phase-change lithography, which uses semiconductor-based resists such as chalcogenide Ge2Sb2Te5 films, was developed to overcome these limitations. Here, instead of chalcogenide, we propose a metallic resist composed of Mg58Cu29Y13 alloy films, which exhibits a considerable difference in etching rate between amorphous and crystalline states. Furthermore, the heat distribution in Mg58Cu29Y13 thin film is better and can be more easily controlled than that in Ge2Sb2Te5 during exposure. We succeeded in fabricating both continuous and discrete patterns on Mg58Cu29Y13 thin films via laser irradiation and wet etching. Our results demonstrate that a metallic resist of Mg58Cu29Y13 is suitable for phase change lithography, and this type of resist has potential due to its outstanding characteristics.