Zheng Huifei, Chen Tengfei, Li Chang, Xu Chun, Ding Cheng, Chen Jun, Ju Sheng, Zhang Zhiwei, Liang Zhipan, Cui Zihan, Zhao Jun
National Center for Liver Cancer, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China,
Cancer Manag Res. 2019 Jan 3;11:443-454. doi: 10.2147/CMAR.S189338. eCollection 2019.
Most recently, circular RNAs (circRNAs) were considered playing regulatory roles in tumor initiation and development. The specific function of circRNAs in hepatocellular carcinoma (HCC) remains unknown. This study was designed to detect specific roles of a circRNA hsa_circ_0079299 in HCC.
The expression of hsa_circ_0079299 in HCC and tumor cell lines was detected using quantitative PCR (qPCR). Cell proliferation, migration, cell cycle and apoptosis after overexpression of the circRNA were measured using cell counting kit-8 (CCK8) assay, colony formation, 5-ethynyl-2'-deoxyuridine (EdU) assay, wound healing assay, transwell culture system and flow cytometry. Western blotting assay detected the protein expression of PI3K/AKT/mTOR signaling pathway and cyclin B1 (CCNB1). Overexpression of the circRNA in vivo was measured by nude mice tumorigenesis.
The expression of hsa_circ_0079299 was lower in HCC tissues. Overexpression of hsa_circ_0079299 suppressed tumor growth in vitro and in vivo, retarded cell cycle progression while had no effect on cell migration and apoptosis. The inhibitory effect of hsa_circ_0079299 was partly mediated by PI3K/AKT/mTOR signaling pathway.
Our study shows that tumor suppressive role of hsa_circ_0079299 in HCC provides new recognition of circRNAs in cancers.
最近,环状RNA(circRNAs)被认为在肿瘤的发生和发展中发挥调节作用。circRNAs在肝细胞癌(HCC)中的具体功能尚不清楚。本研究旨在检测环状RNA hsa_circ_0079299在HCC中的特定作用。
采用定量PCR(qPCR)检测hsa_circ_0079299在HCC组织及肿瘤细胞系中的表达。使用细胞计数试剂盒-8(CCK8)检测、集落形成实验、5-乙炔基-2'-脱氧尿苷(EdU)检测、伤口愈合实验、Transwell培养系统和流式细胞术检测circRNA过表达后的细胞增殖、迁移、细胞周期和凋亡情况。蛋白质印迹法检测PI3K/AKT/mTOR信号通路和细胞周期蛋白B1(CCNB1)的蛋白表达。通过裸鼠成瘤实验检测circRNA在体内的过表达情况。
hsa_circ_0079299在HCC组织中的表达较低。hsa_circ_0079299的过表达在体外和体内均抑制肿瘤生长,阻滞细胞周期进程,但对细胞迁移和凋亡无影响。hsa_circ_0079299的抑制作用部分由PI3K/AKT/mTOR信号通路介导。
我们的研究表明,hsa_circ_0079299在HCC中具有肿瘤抑制作用,这为circRNAs在癌症中的作用提供了新的认识。