Circ_0060055 Promotes the Growth, Invasion, and Radioresistance of Glioblastoma by Targeting MiR-197-3p/API5 Axis

被引:11
作者
Yuan, Jinjin [1 ]
Liu, Zongwen [1 ]
Liu, Junqi [2 ]
Fan, Ruitai [2 ]
机构
[1] Zhengzhou Univ, Dept Radiotherapy, Affiliated Hosp 2, Zhengzhou 450000, Henan, Peoples R China
[2] Zhengzhou Univ, Dept Radiotherapy, Affiliated Hosp 1, 1 Jianshe East Rd, Zhengzhou 450000, Henan, Peoples R China
关键词
Glioblastoma; Circ_0060055; MiR-197-3p; API5; CIRCULAR RNA; PROGRESSION; CANCER;
D O I
10.1007/s12640-022-00548-w
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Circular RNA (circRNA) has been shown to be involved in the regulation of human disease progression. Our study aims to reveal the role of circ_0060055 in the progression of glioblastoma (GBM) and its potential molecular mechanism. The expression of circ_0060055, microRNA (miR)-197-3p, and apoptosis inhibitor 5 (API5) was determined by quantitative real-time PCR. GBM cell proliferation, apoptosis, and invasion were assessed using cell counting kit 8 assay, colony formation assay, EdU assay, flow cytometry, and transwell assay. Besides, the radiosensitivity of cells also was assessed using colony formation assay. The interaction between miR-197-3p and circ_0060055 or API5 was analyzed by dual-luciferase reporter assay and RNA pull-down assay. Animal experiments were conducted to measure the effect of circ_0060055 on GBM tumor growth and radiosensitivity in vivo. Circ_0060055 was overexpressed in GBM tumor tissues and cells, and its silencing suppressed GBM cell proliferation and invasion, while promoted apoptosis and radiosensitivity. In terms of mechanism, circ_0060055 could interact with miR-197-3p, and miR-197-3p could target API5. API5 expression also could be positively regulated by circ_0060055. Function experiments suggested that miR-197-3p inhibitor abolished the effect of circ_0060055 knockdown on GBM cell growth, invasion, and radiosensitivity. MiR-197-3p repressed GBM cell progression and improved radiosensitivity, and this effect was eliminated by API5 upregulation. In vivo experiments confirmed that circ_0060055 knockdown reduced GBM tumor growth and enhanced the radiosensitivity of tumors. This study revealed that circ_0060055 contributed to GBM progression and radioresistance through miR-197-3p/API5 pathway, providing a potential target for GBM treatment.
引用
收藏
页码:1292 / 1303
页数:12
相关论文
共 31 条
[21]   Ten-year survival in glioblastoma. A systematic review [J].
Tykocki, Tomasz ;
Eltayeb, Mohamed .
JOURNAL OF CLINICAL NEUROSCIENCE, 2018, 54 :7-13
[22]   MiR-224 expression increases radiation sensitivity of glioblastoma cells [J].
Upraity, Shailendra ;
Kazi, Sadaf ;
Padul, Vijay ;
Shirsat, Neelam Vishwanath .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2014, 448 (02) :225-230
[23]   Identification of low-dose radiation-induced exosomal circ- METRN and miR-4709-3p/GRB14/PDGFRα pathway as a key regulatory mechanism in Glioblastoma progression and radioresistance: Functional validation and clinical theranostic significance [J].
Wang, Xinxin ;
Cao, Qinchen ;
Shi, Yonggang ;
Wu, Xiaolong ;
Mi, Yin ;
Liu, Ke ;
Kan, Quancheng ;
Fan, Ruitai ;
Liu, Zhangsuo ;
Zhang, Mingzhi .
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2021, 17 (04) :1061-1078
[24]   Circular RNAs in renal cell carcinoma: implications for tumorigenesis, diagnosis, and therapy [J].
Wang, Ying ;
Zhang, Yunjing ;
Wang, Ping ;
Fu, Xianghui ;
Lin, Weiqiang .
MOLECULAR CANCER, 2020, 19 (01)
[25]  
Wang ZM, 2010, MED SCI MONITOR, V16, pCR357
[26]  
Wirsching Hans-Georg, 2016, Handb Clin Neurol, V134, P381, DOI 10.1016/B978-0-12-802997-8.00023-2
[27]   miR-197-3p reduces epithelial-mesenchymal transition by targeting ABCA7 in ovarian cancer cells [J].
Xie, Weiquan ;
Shui, Chengyu ;
Fang, Xiping ;
Peng, Yuqiu ;
Qin, Li .
3 BIOTECH, 2020, 10 (08)
[28]   Overexpressed circ_0029426 in glioblastoma forecasts unfavorable prognosis and promotes cell progression by sponging miR-197 [J].
Zhang, Guifang ;
Sun, Weibo ;
Zhu, Liangfu ;
Feng, Yingpu ;
Wu, Liheng ;
Li, Tianxiao .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2019, 120 (06) :10295-10302
[29]   CircABCC3 knockdown inhibits glioblastoma cell malignancy by regulating miR-770-5p/SOX2 axis through PI3K/AKT signaling pathway [J].
Zhang, Huan ;
Xu, Wei .
BRAIN RESEARCH, 2021, 1764
[30]   Up-Regulation of circEIF6 Contributes to Pancreatic Cancer Development Through Targeting miR-557/SLC7A11/PI3K/AKT Signaling [J].
Zhang, Tiequan ;
Li, Mi ;
Lu, Haofeng ;
Peng, Tao .
CANCER MANAGEMENT AND RESEARCH, 2021, 13 :247-258