CircRNA hsa_circRNA_0001776 inhibits proliferation and promotes apoptosis in endometrial cancer via downregulating LRIG2 by sponging miR-182

被引:35
作者
Jia, Youjuan [1 ]
Liu, Meijuan [2 ]
Wang, Shuxia [3 ]
机构
[1] Weifang Peoples Hosp, Dept Gynecol, 151 Guangwen St, Weifang 261041, Shandong, Peoples R China
[2] Yantai Yuhuangding Hosp, Dept Ultrasound, Yantai 264000, Shandong, Peoples R China
[3] Weifang Peoples Hosp, Dept Obstet, Weifang 261041, Shandong, Peoples R China
关键词
Endometrial cancer; hsa_circRNA_0001776; miR-182; LRIG2; CIRCULAR RNA; CELLS; EXPRESSION; INVASION;
D O I
10.1186/s12935-020-01437-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Endometrial cancer (EC) is a common malignancy of the female reproductive system. Circular RNAs (circRNAs) were demonstrated to exert critical roles in cancers, including EC. This study aimed to investigate the effects of hsa_circRNA_0001776 (circ_0001776) on EC. Methods Real-time quantitative PCR (RT-qPCR) was used to measure circ_0001776, microRNA-182 (miR-182) and leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) expression. The diagnostic and prognostic values of circ_0001776 were identified by receiver operating characteristic (ROC) curve analysis and survival analysis, respectively. RNase R digestion was used to characterize circ_0001776, and the localization of circ_0001776 was evaluated by cell fractionation assay. Then, cell counting kit-8 (CCK-8), colony formation, and flow cytometry analysis were used to detect cell proliferation and apoptosis, respectively. The real-time glycolytic rate (ECAR) and lactate production were measured by extracellular flux analysis and a lactate assay kit, respectively. Bioinformatics analysis and dual-luciferase reporter assay were used to determine the interaction among circ_0001776, miR-182 and LRIG2. The protein expression of LRIG2 was determined by western blot. Moreover, circ_0001776 overexpression vector was used to upregulate circ_0001776 expression in an animal tumor model. Results Circ_0001776 and LRIG2 were downregulated, while miR-182 was upregulated in EC tissues and cells. Low expression of circ_0001776 was correlated with the 5-year survival rate of EC patients. Upregulated circ_0001776 markedly attenuated cell proliferation and glycolysis, and enhanced cell apoptosis. Besides, circ_0001776 sponged miR-182 to regulate LRIG2 expression. Circ_0001776 could suppress EC progression by miR-182/LRIG2 axis. Furthermore, we also found that circ_0001776 significantly inhibited tumor growth in vivo. Conclusion Our results confirmed that circ_0001776 inhibited EC tumorigenesis and progression via miR-182/LRIG2 axis, providing a potential therapeutic target for EC.
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页数:13
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共 36 条
[1]   2 PATHOGENETIC TYPES OF ENDOMETRIAL CARCINOMA [J].
BOKHMAN, JV .
GYNECOLOGIC ONCOLOGY, 1983, 15 (01) :10-17
[2]   Circular RNA Pleiotrophin promotes carcinogenesis in glioma via regulation of microRNA-122/SRY-box transcription factor 6 axis [J].
Chen, Chen ;
Deng, Lu ;
Nie, De-Kang ;
Jia, Feng ;
Fu, Lin-Shan ;
Wan, Zheng-Qiang ;
Lan, Qing .
EUROPEAN JOURNAL OF CANCER PREVENTION, 2020, 29 (02) :165-173
[3]   Regulation of circRNA biogenesis [J].
Chen, Ling-Ling ;
Yang, Li .
RNA BIOLOGY, 2015, 12 (04) :381-388
[4]   Using circular RNA hsa_circ_0000190 as a new biomarker in the diagnosis of gastric cancer [J].
Chen, Shijun ;
Li, Tianwen ;
Zhao, Qianfu ;
Xiao, Bingxiu ;
Guo, Junming .
CLINICA CHIMICA ACTA, 2017, 466 :167-171
[5]   Effect of metformin use on the risk and prognosis of endometrial cancer: a systematic review and meta-analysis [J].
Chu, Danxia ;
Wu, Jie ;
Wang, Kaili ;
Zhao, Mengling ;
Wang, Chunfang ;
Li, Liuxia ;
Guo, Ruixia .
BMC CANCER, 2018, 18
[6]   Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182 [J].
Devor, Eric J. ;
Schickling, Brandon M. ;
Reyes, Henry D. ;
Warrier, Akshaya ;
Lindsay, Brittany ;
Goodheart, Michael J. ;
Santillan, Donna A. ;
Leslie, Kimberly K. .
ONCOLOGY REPORTS, 2016, 35 (04) :2461-2465
[7]   Endometrial carcinoma [J].
Di Cristofano, Antonio ;
Ellenson, Lora Hedrick .
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2007, 2 :57-85
[8]   MicroRNAs in Cancer [J].
Di Leva, Gianpiero ;
Garofalo, Michela ;
Croce, Carlo M. .
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 9, 2014, 9 :287-314
[9]   Circular RNA and its mechanisms in disease: From the bench to the clinic [J].
Han, Bing ;
Chao, Jie ;
Yao, Honghong .
PHARMACOLOGY & THERAPEUTICS, 2018, 187 :31-44
[10]   Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling [J].
Han, Jianjun ;
Zhang, Lu ;
Guo, Hui ;
Wysham, Weiya Z. ;
Roque, Dario R. ;
Willson, Adam K. ;
Sheng, Xiugui ;
Zhou, Chunxiao ;
Bae-Jump, Victoria L. .
GYNECOLOGIC ONCOLOGY, 2015, 138 (03) :668-675