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
[1]   Management of glioblastoma [J].
Aoki, Tomokazu ;
Hashimoto, Nobuo ;
Matsutani, Masao .
EXPERT OPINION ON PHARMACOTHERAPY, 2007, 8 (18) :3133-3146
[2]   Silencing BMI1 eliminates tumor formation of pediatric glioma CD133+ cells not by affecting known targets but by down-regulating a novel set of core genes [J].
Baxter, Patricia A. ;
Lin, Qi ;
Mao, Hua ;
Kogiso, Mari ;
Zhao, Xiumei ;
Liu, Zhigang ;
Huang, Yulun ;
Voicu, Horatiu ;
Gurusiddappa, Sivashankarappa ;
Su, Jack M. ;
Adesina, Adekunle M. ;
Perlaky, Laszlo ;
Dauser, Robert C. ;
Leung, Hon-chiu Eastwood ;
Muraszko, Karin M. ;
Heth, Jason A. ;
Fan, Xing ;
Lau, Ching C. ;
Man, Tsz-Kwong ;
Chintagumpala, Murali ;
Li, Xiao-Nan .
ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2014, 2
[3]  
Bousquet Guilhem, 2019, Oncotarget, V10, P6577, DOI 10.18632/oncotarget.27312
[4]   Targeting Glioblastoma Tumor Microenvironment [J].
Butler, Megan ;
Prasad, Sahdeo ;
Srivastava, Sanjay K. .
TUMOR MICROENVIRONMENTS IN ORGANS: FROM THE BRAIN TO THE SKIN, PT B, 2020, 1296 :1-9
[5]   Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer [J].
Cho, Hanbyoul ;
Chung, Joon-Yong ;
Song, Kwon-Ho ;
Noh, Kyung Hee ;
Kim, Bo Wook ;
Chung, Eun Joo ;
Ylaya, Kris ;
Kim, Jin Hee ;
Kim, Tae Woo ;
Hewitt, Stephen M. ;
Kim, Jae-Hoon .
BMC CANCER, 2014, 14
[6]   Regulation of microRNA miR-197-3p/CDC28 protein kinase regulatory subunit 1B (CKS1B) axis by Circular RNA hsa_circ_0000285 promotes glioma progression [J].
Deng, Tao ;
Liu, Yang ;
Yang, Yanlong ;
Yuan, Leyong ;
Liu, Fangfang ;
Wang, Xiaobo ;
Zhang, Qiuying ;
Xie, Mingshui .
BIOENGINEERED, 2022, 13 (03) :4757-4772
[7]   Identification of circRNA-miRNA-mRNA regulatory network in gastric cancer by analysis of microarray data [J].
Guan, Yong-jun ;
Ma, Jian-ying ;
Song, Wei .
CANCER CELL INTERNATIONAL, 2019, 19 (1)
[8]   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
[9]   Circular RNA - New member of noncoding RNA with novel functions [J].
Hsiao, Kuei-Yang ;
Sun, H. Sunny ;
Tsai, Shaw-Jenq .
EXPERIMENTAL BIOLOGY AND MEDICINE, 2017, 242 (11) :1136-1141
[10]   circRNA derived from CLSPN (circCLSPN) is an oncogene in human glioblastoma multiforme by regulating cell growth, migration and invasion via ceRNA pathway [J].
Hu, Tao ;
Lei, Dan ;
Zhou, Jianhua ;
Zhang, Bo .
JOURNAL OF BIOSCIENCES, 2021, 46 (03)