HAND2-AS1通过微小RNA海绵抑制胃腺癌细胞增殖和有氧糖酵解。
HAND2-AS1 Inhibits Gastric Adenocarcinoma Cells Proliferation and Aerobic Glycolysis via miRNAs Sponge.
作者信息
Xu Zhiyuan, Lv Hang, Wang Yiping, Hu Can, Chen Shangqi, Du Yian, Shi Chengwei, Cheng Xiangdong
机构信息
Department of Gastric Surgery, Institute of Cancer and Basic Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, People's Republic of China.
Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diagnosis and Treatment of Digestive System Tumor, Hangzhou 300020, Zhejiang, People's Republic of China.
出版信息
Cancer Manag Res. 2020 May 1;12:3053-3068. doi: 10.2147/CMAR.S222878. eCollection 2020.
OBJECTIVE
To study the effect of lncRNA HAND2-AS1 on gastric adenocarcinoma (GA) cell property and explore its specific mechanism.
METHODS
Data on stomach adenocarcinoma (STAD) were analyzed to screen differentially expressed lncRNA HAND2-AS1. RNA22-HAS database and dual luciferase reporter assay were applied to confirm the target relationship between HAND2-AS1/HIF3A and miR-184. The HAND2-AS1 and miR-184 expressions in tissue or cells were determined by qRT-PCR and Western blot. Besides, after GA cells (AGS) cultured in normoxic and hypoxic condition, phosphoenolpyruvate (PEP) and lactic acid were quantified by Phosphoenolpyruvate Fluorometric Assay Kit and Lactic Acid Detection kit, respectively. Additionally, colony formation assay, transwell invasion and migration assays were used to evaluate the abilities of cell invasion, migration, and proliferation in distinct conditions.
RESULTS
The HAND2-AS1 and HIF3A expressions were down-regulated and miR-184 expression was up-regulated in GA tissues and cells. Dual luciferase reporter assay confirmed HAND2-AS1 and HIF3A were targeted by miR-184. AGS cell proliferation abilities were restrained by HAND2-AS1 and HIF3A overexpression and enhanced by miR-184, as well as migration and invasion abilities. In addition, HAND2-AS1 rescued enhanced AGS cell proliferation, cell migration, cell invasion abilities and glycolytic process caused by hypoxia via miR-184/HIF3A.
CONCLUSION
LncRNA HAND2-AS1 could inhibit GA cell proliferation, migration and invasion abilities and glycolytic process induced by hypoxia through miR-184/HIF3A signaling.
目的
研究长链非编码RNA HAND2-AS1对胃腺癌（GA）细胞特性的影响，并探讨其具体机制。
方法
分析胃腺癌（STAD）数据以筛选差异表达的长链非编码RNA HAND2-AS1。应用RNA22-HAS数据库和双荧光素酶报告基因检测法来确认HAND2-AS1/HIF3A与miR-184之间的靶向关系。通过qRT-PCR和蛋白质免疫印迹法检测组织或细胞中HAND2-AS1和miR-184的表达。此外，在常氧和低氧条件下培养GA细胞（AGS）后，分别使用磷酸烯醇丙酮酸荧光定量检测试剂盒和乳酸检测试剂盒对磷酸烯醇丙酮酸（PEP）和乳酸进行定量。另外，采用集落形成实验、Transwell侵袭和迁移实验来评估不同条件下细胞的侵袭、迁移和增殖能力。
结果
在GA组织和细胞中，HAND2-AS1和HIF3A的表达下调，miR-184的表达上调。双荧光素酶报告基因检测证实HAND2-AS1和HIF3A是miR-184的靶标。HAND2-AS1和HIF3A过表达抑制了AGS细胞的增殖能力，而miR-184则增强了其增殖能力，同时也增强了迁移和侵袭能力。此外，HAND2-AS1通过miR-184/HIF3A挽救了低氧诱导的AGS细胞增殖、细胞迁移、细胞侵袭能力及糖酵解过程的增强。
结论
长链非编码RNA HAND2-AS1可通过miR-184/HIF3A信号通路抑制GA细胞增殖、迁移和侵袭能力以及低氧诱导的糖酵解过程。
Zotero 插件