ASAP1 protein macromolecule promotes the growth and development of gastric cancer cells and the remodeling of F-actin cytoskeleton: Expression of VEGF and HIF-1 α proteins

IF 7.7 1区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hongyu Gao , Ling Qin , Huawen Shi , Haibin Song , Zhiguo Li , Yingwei Xue , Tianbo Liu
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引用次数: 0

Abstract

ASAP1 (Ankyrin Repeat and PH Domain 1) is a macromolecular regulatory protein, which has been shown to play an important role in a variety of tumors in recent years. Gastric cancer (GC), as a highly lethal malignancy worldwide, is in urgent need of new biomarkers and therapeutic targets. Tissue samples from multiple gastric cancer patients were collected and analyzed through TCGA and GEO databases. The expression of ASAP1 and its correlation with clinicopathological features were evaluated by tissue microarray and immunohistochemical staining. The biological function of ASAP1 was analyzed by cell line culture, Westernblot and real-time fluorescence quantitative PCR. Cell migration, invasion, in vitro tube formation and xenotransplantation models were performed to detect the effects of ASAP1 on tumor growth and angiogenesis. The cytoskeletal remodeling process was evaluated by luciferase reporting assay and Phalloidin staining assay. It has been found that the expression of ASAP1 in gastric cancer tissues is significantly increased, and it is closely related to the prognosis of patients. The expression of ASAP1 was positively correlated with the levels of VEGF and HIF-1 alpha. The elimination of ASAP1 significantly inhibited the migration, invasion and angiogenesis of gastric cancer cells. In xenograft experiments, ASAP1 promoted tumor growth and angiogenesis. miR-let-7a-5p can affect the migration, invasion and F-actin bundle formation of gastric cancer cells by targeting ASAP1.
ASAP1蛋白大分子促进胃癌细胞生长发育和f -肌动蛋白骨架重塑:VEGF和HIF-1 α蛋白的表达
ASAP1 (Ankyrin Repeat and PH Domain 1)是一种大分子调控蛋白,近年来被证明在多种肿瘤中发挥重要作用。胃癌作为世界范围内的高致死率恶性肿瘤,迫切需要新的生物标志物和治疗靶点。收集多例胃癌患者的组织样本,通过TCGA和GEO数据库进行分析。采用组织芯片和免疫组化染色检测ASAP1的表达及其与临床病理特征的相关性。通过细胞系培养、Westernblot和实时荧光定量PCR分析ASAP1的生物学功能。通过细胞迁移、侵袭、体外成管和异种移植模型检测ASAP1对肿瘤生长和血管生成的影响。采用荧光素酶报告法和Phalloidin染色法评价细胞骨架重塑过程。研究发现,ASAP1在胃癌组织中的表达明显升高,与患者的预后密切相关。ASAP1的表达与VEGF、HIF-1 α水平呈正相关。消除ASAP1可显著抑制胃癌细胞的迁移、侵袭和血管生成。在异种移植实验中,ASAP1促进肿瘤生长和血管生成。miR-let-7a-5p可通过靶向ASAP1影响胃癌细胞的迁移、侵袭及F-actin束的形成。
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来源期刊
International Journal of Biological Macromolecules
International Journal of Biological Macromolecules 生物-生化与分子生物学
CiteScore
13.70
自引率
9.80%
发文量
2728
审稿时长
64 days
期刊介绍: The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.
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