Metastasis is the most significant process affecting the clinical management of cancer patients and occurs in multiple sequential steps. However, the molecular pathways underlying each step still remain obscure. Recent research has shown that there is a microRNA (miRNA) network that functions as a regulator of tumor metastasis. In this paper, we review the role of miRNAs in tumor metastasis, including control of epithelial-mesenchymal transition, regulation of metastasis-associated genes and epigenetic alterations. More information on miRNAs will promote a better understanding of the molecular mechanism of metastasis.
Zinc finger protein 139(ZNF139), a member of zinc finger protein family, is a transcription factor. Our previous research showed ZNF139 was overexpressed in gastric cancer cells. The purpose of present study is to explore impact and mechanism of ZNF139 on metastasis by regulating invasive ability of gastric cancer cells.Quantitative RT-PCR(QRT-PCR) and Western blot were applied for detection of ZNF139 expression in gastric cancer tissues, adjacent cancer tissues, metastatic lymph nodes, gastric cancer cell lines SGC7901 and BGC823 and gastric epithelial cell line GES-1; siRNA specific to ZNF139 was synthesized and then transfected into gastric cancer cell line BGC823; wound healing assay and Transwell assay were used to observe impact of ZNF139-siRNA after being transfected into BGC823 on its invasion and migration; changes in expression of invasion and migration-related genes MMP-2, MMP-9, ICAM-1 and TIMP1 were detected before and after transfection. Gelatin zymogrphy assay were applied to determine the MMP activities. Statistical analysis was based on the SPSS11.5 software.Expression of ZNF139 in gastric adenocarcinoma tissues and cells was significantly higher than the expression in the adjacent cancer tissues, but lower than the expression in the metastatic lymph nodes; ZNF139 expression was present in gastric cancer cell lines, and the expression level was higher than that in normal gastric epithelial cells lines. ZNF139-siRNA significantly inhibited the invasion and migration activity of gastric cancer cell line BGC823. 48h after ZNF139-siRNA was transfected into gastric cancer cell line BGC823, expression and activity of invasion-related genes MMP-2, MMP-9, ICAM-1 mRNA and protein were significantly inhibited, while expressions of TIMP-1 mRNA and protein were significantly increased. At the same time, the gelatinase activities of MMP2 and MMP9 were decreased by ZNF139 interference.ZNF139 was overexpressed in gastric cancer cells, and the expression was further enhanced in the metastasis process. Knocking down ZNF139 expression in gastric cancer cells could effectively reduce gastric cancer cell invasion and migration ability, and this process might play a role by regulating MMP-TIMP balance. Key words: gastric cancer, zinc finger protein 139(ZNF139), migration, invasion, RNA interference technologyGastric cancer is currently the second leading cancer killer in the world. High incidence of gastric cancer exists in east Asia, which is also the leading cause of death in malignant tumor in China. Gastric cancer has strong ability for proliferation, invasion and metastasis, which is one of the important factors that lead to poor prognosis. A variety of genes in tumor cells and their expression products play an important role in the invasion and metastasis process of gastric cancer [1][2][3][4]. It has been a hotspot to treat gastric cancer by inhibiting invasion and migration capability of gastric cancer cells, and the study has made some achievements [5][6][7]. But there has yet not been a breakthrough in the...
Summary Improving litter size at birth (TNB) and the number of piglets born alive (NBA) are the main breeding goals related to litter traits, which are economically important. A better understanding of genetic architecture underlying TNB and NBA traits could increase pig production efficiency. However, most previous studies on these traits focus on additive genetic effects, while epistatic interactions underlying TNB and NBA traits has not yet been well investigated, which are essential to understand how traits‐related genes interact. Herein, we conducted genome scans of epistatic interactions underlying TNB and NBA traits in a total of 150 Chinese indigenous pigs (75 Jinhua and 75 Shengxian Spotted pigs) with high throughput genomic data. Based on SNPs with high interaction values and connectivity scores, we identified eight promising candidate genes (AKT2, TSC1, MTOR, PIK3R5, TIAM1, FGF14, RALB and ROR2) potentially associated with litter traits in pigs. Moreover, the underlying pathways, e.g., calcium ion transport, pointed out their roles in litter size‐related traits. Our findings provide new insight into genetic architecture of litter traits in pigs and will benefit economic profits in pig production.
Background:The rapid development of sequencing technology and simultaneously the availability of large quantities of sequence data provides an unprecedented opportunity for researchers to conduct studies to detect rare variants associated with the disease. However, none of current existing statistical methods has uniform power in all scenarios because they more or less are affected by nonfunctional variants and variants with opposite effect. The present study focuses on identifying rare variant associated with the disease.Results: we present a robust approach to identify rare variant using weighted entropy theory.This approach here takes the proportion of the minor allele among all k variants as its probability distribution, which reduces the noise incurred by non-causal variants, and uses a weight to strike a balance between deleterious rare variants and protective rare variants, which makes our method impacted less by variants with opposite effect. Through simulation studies, we investigate the performance of our method for rare variant association analyses as well as for common variant association analyses and compared it with Burden test and the SKAT-O test. Simulation study show that the proposed method is valid and outperform two existing methods. Meanwhile, the proposed method is affected slightly by non-causal variants and opposite effect variants with high and stable power for various paraments set. Conclusions:We conclude that the proposed method here can be used effectively to detect rare variant associated with the disease.
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