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环状RNA circ_0000517通过miR-326/IGF1R轴调控肝细胞癌的发展。

Circular RNA circ_0000517 regulates hepatocellular carcinoma development via miR-326/IGF1R axis.

作者信息

He Shuwei, Yang Jianzeng, Jiang Shitao, Li Yuan, Han Xingmin

机构信息

Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450000 Henan China.

出版信息

Cancer Cell Int. 2020 Aug 25;20:404. doi: 10.1186/s12935-020-01496-1. eCollection 2020.

DOI:10.1186/s12935-020-01496-1
PMID:32863763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7448484/
Abstract

BACKGROUND

Circular RNAs (circRNAs) play vital roles in hepatocellular carcinoma development. However, the role and mechanism of circRNA hsa_circ_0000517 (circ_0000517) in hepatocellular carcinoma development were largely unknown.

METHODS

45 paired tumor and adjacent nontumor samples were collected from hepatocellular carcinoma patients. The levels of circ_0000517, miR-326 and insulin-like growth factor type 1 receptor (IGF1R) were detected via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, colony ability, migration, invasion and glycolysis were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, western blot, transwell assay, glucose consumption, lactate production or adenosine triphosphate (ATP) production. The target correlation between miR-326 and circ_0000517 or IGF1R was analyzed via dual-luciferase reporter analysis. The function of circ_0000517 in vivo was assessed via xenograft model.

RESULTS

circ_0000517 expression was elevated in hepatocellular carcinoma tissues and cell lines. circ_0000517 knockdown suppressed cell viability, colony formation, migration, invasion and glycolysis. miR-326 was sponged via circ_0000517 and miR-326 knockdown reversed the effect of circ_0000517 silence on hepatocellular carcinoma development. miR-326 overexpression inhibited hepatocellular carcinoma development through targeting IGF1R. circ_0000517 knockdown decreased IGF1R expression by modulating miR-326. circ_0000517 downregulation reduced xenograft tumor growth.

CONCLUSION

circ_0000517 knockdown repressed hepatocellular carcinoma development in vitro and in vivo by modulating miR-326 and IGF1R.

摘要

背景

环状RNA（circRNAs）在肝细胞癌发展中发挥着重要作用。然而，circRNA hsa_circ_0000517（circ_0000517）在肝细胞癌发展中的作用及机制尚不清楚。

方法

收集45例肝细胞癌患者的肿瘤组织及其配对的癌旁非肿瘤组织样本。通过定量逆转录聚合酶链反应或蛋白质免疫印迹法检测circ_0000517、miR-326和胰岛素样生长因子1型受体（IGF1R）的水平。通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）法、集落形成实验、蛋白质免疫印迹法、Transwell实验、葡萄糖消耗实验、乳酸生成实验或三磷酸腺苷（ATP）生成实验评估细胞活力、集落形成能力、迁移、侵袭及糖酵解情况。通过双荧光素酶报告基因分析检测miR-326与circ_0000517或IGF1R之间的靶向关系。通过异种移植模型评估circ_0000517在体内的功能。

结果

circ_0000517在肝细胞癌组织和细胞系中表达升高。敲低circ_0000517可抑制细胞活力、集落形成、迁移、侵袭及糖酵解。circ_0000517可吸附miR-326，敲低miR-326可逆转circ_0000517沉默对肝细胞癌发展的影响。过表达miR-326可通过靶向IGF1R抑制肝细胞癌发展。敲低circ_0000517可通过调节miR-326降低IGF1R表达。下调circ_0000517可减少异种移植瘤的生长。

结论

敲低circ_0000517可通过调节miR-326和IGF1R在体外和体内抑制肝细胞癌发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/4d5350e8b2ec/12935_2020_1496_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/dd9e074250b5/12935_2020_1496_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/d20eb811a5f6/12935_2020_1496_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/4d5350e8b2ec/12935_2020_1496_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/dd9e074250b5/12935_2020_1496_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/4115cb4f5e82/12935_2020_1496_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/2eac76873a49/12935_2020_1496_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/a8012b956d86/12935_2020_1496_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/1c853f419c61/12935_2020_1496_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/b43285c4b4e7/12935_2020_1496_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/d20eb811a5f6/12935_2020_1496_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dc9/7448484/4d5350e8b2ec/12935_2020_1496_Fig8_HTML.jpg

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