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靶向SPARC的MiR-1275促进藤黄酸诱导的胃癌抑制作用。

MiR-1275 Targeting SPARC Promotes Gambogic Acid-Induced Inhibition of Gastric Cancer.

作者信息

Cai Ang, Xia Pengfei, Zhou Xiaokang, He Yao, Lv Jun

机构信息

Department of Oncology, Wuhan Hospital of Traditional Chinese Medicine, No. 49, Lihuangpi Road, Jiang'an District, Wuhan, 430014, Hubei, People's Republic of China.

Department of Gastric Diseases and Liver-Gallbladder (Department of Gastroenterology), Wuhan Hospital of Traditional Chinese Medicine, Wuhan, 430014, Hubei, People's Republic of China.

出版信息

Biochem Genet. 2023 Dec;61(6):2481-2495. doi: 10.1007/s10528-023-10381-1. Epub 2023 Apr 28.

Abstract

Gambogic acid (GA) has been observed to effectively impede the progression of numerous types of cancers. In this study, we investigated the effects of miR-1275 and Secreted Protein Acidic and Cysteine Rich (SPARC) on GA in gastric cancer (GC). miR-1275 and SPARC expression were determined in GC cell lines and tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between miR-1275 and SPARC expression was ascertained using Pearson's correlation coefficient. Cell proliferation was assessed using the cell counting kit-8 (CCK-8) assay. The Transwell assay was conducted to examine cell migration. A dual-luciferase reporter assay was used to verify the regulatory relationship between miR-1275 and SPARC. The levels of SPARC, Bcl-2, and Bax proteins were estimated using western blotting. To verify the effects of GA on the growth of GC cells in vivo, a tumorigenesis experiment was performed in nude mice. GA suppressed GC cell viability and migration, facilitated apoptosis, and inhibited tumor growth in vivo and in vitro. Low levels of miR-1275 been observed in GC cell lines and tissues. GA-treated GC cells manifested high miR-1275 levels. In functional experiments, miR-1275 enhanced the influence of GA on cell apoptosis, migration, and proliferation. Furthermore, GA treatment suppressed SPARC upregulation in GC cell lines and tissues. Pearson's correlation coefficient revealed that miR-1275 expression negatively correlated with SPARC expression. Mechanistically, miR-1275 promoted growth inhibition in GA-treated GC cells by targeting SPARC. Our study indicates that miR-1275 enhances the suppressive effect of GA on GC progression by inhibiting SPARC expression. Through this study, we contribute to the knowledge of a new mechanism by which GA suppresses GC progression.

摘要

藤黄酸(GA)已被观察到能有效阻碍多种癌症的进展。在本研究中,我们调查了miR - 1275和富含酸性和半胱氨酸的分泌蛋白(SPARC)对胃癌(GC)中GA的影响。使用逆转录定量聚合酶链反应(RT - qPCR)测定GC细胞系和组织中miR - 1275和SPARC的表达。使用Pearson相关系数确定miR - 1275与SPARC表达之间的相关性。使用细胞计数试剂盒 - 8(CCK - 8)测定法评估细胞增殖。进行Transwell测定以检查细胞迁移。使用双荧光素酶报告基因测定法验证miR - 1275与SPARC之间的调控关系。使用蛋白质印迹法估计SPARC、Bcl - 2和Bax蛋白的水平。为了验证GA对体内GC细胞生长的影响,在裸鼠中进行了肿瘤发生实验。GA抑制了GC细胞的活力和迁移,促进了细胞凋亡,并在体内和体外抑制了肿瘤生长。在GC细胞系和组织中观察到低水平的miR - 1275。GA处理的GC细胞表现出高miR - 1275水平。在功能实验中,miR - 1275增强了GA对细胞凋亡、迁移和增殖的影响。此外,GA处理抑制了GC细胞系和组织中SPARC的上调。Pearson相关系数显示miR - 1275表达与SPARC表达呈负相关。机制上,miR - 1275通过靶向SPARC促进GA处理的GC细胞的生长抑制。我们的研究表明,miR - 1275通过抑制SPARC表达增强了GA对GC进展的抑制作用。通过这项研究,我们有助于了解GA抑制GC进展的新机制。

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