Circular RNA circ_0020123 promotes non-small cell lung cancer progression by sponging miR-590-5p to regulate THBS2

被引:35
作者
Wang, Liang [1 ]
Zhao, Lantao [1 ]
Wang, Yonghong [1 ]
机构
[1] Lianyungang Second Peoples Hosp, Dept Thorac Surg, 41 Hailian East Rd, Lianyungang 222006, Jiangsu, Peoples R China
关键词
NSCLC; Circ_0020123; miR-590-5p; THBS2; EXPRESSION; MIGRATION;
D O I
10.1186/s12935-020-01444-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background The incidence and death rate of non-small cell lung cancer (NSCLC) in China ranks the first among the malignant tumors. Circular RNA (circRNA) was reported to be involved in the progression of NSCLC. Our study aimed to investigate the underlying mechanism of circ_0020123 in NSCLC progression. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0020123, miR-590-5p and Thrombospondin 2 (THBS2) in NSCLC tissues and cells. Cell proliferation and migration were examined by Cell Counting Kit-8 (CCK-8) assay and Transwell assay, respectively. Flow cytometry assay was used to detect the apoptosis of NSCLC cells. The protein levels of Ki-67, matrix metalloprotein-9 (MMP-9), Cleaved-caspase9 (Cleaved-casp9) and THBS2 were detected by Western blot. The targets of circ_0020123 and miR-590-5p were predicted by starBase 3.0 and TargetScan, and then confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The animal experiment showed the effect of circ_0020123 on tumor growth in vivo. Results The expression of circ_0020123 was upregulated in NSCLC tissues and cells. Functionally, circ_0020123 downregulation inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. Interestingly, circ_0020123 directly targeted miR-590-5p, and inhibition of miR-590-5p reversed the knockdown effects of circ_0020123 on NSCLC cells. More importantly, THBS2 was a target of miR-590-5p, and THBS2 overexpression reversed the effects of circ_0020123 knockdown on cell proliferation, migration and apoptosis in NSCLC cells. Finally, suppression of circ_0020123 inhibited tumor growth in vivo through miR-590-5p/THBS2 axis. Conclusion Circular RNA circ_0020123 regulated THBS2 by sponging miR-590-5p to promote cell proliferation and migration and inhibit cell apoptosis in NSCLC cells.
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页数:11
相关论文
共 33 条
[1]   Insulinoma-associated protein 1 is a novel diagnostic marker of small cell lung cancer in bronchial brushing and cell block cytology from pleural effusions: Validity and reliability with cutoff value [J].
Abe, Hideyuki ;
Takase, Yorihiko ;
Sadashima, Eiji ;
Fukumitsu, Chihiro ;
Murata, Kazuya ;
Ito, Takaaki ;
Kawahara, Akihiko ;
Naito, Yoshiki ;
Akiba, Jun .
CANCER CYTOPATHOLOGY, 2019, 127 (09) :598-605
[2]  
[Anonymous], 2016, SCI REP UK
[3]   Circular RNA: New Regulatory Molecules [J].
Belousova, E. A. ;
Filipenko, M. L. ;
Kushlinskii, N. E. .
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE, 2018, 164 (06) :803-815
[4]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[5]   Downregulation of SOX2 may be targeted by miR-590-5p and inhibits epithelial-to-mesenchymal transition in non-small-cell lung cancer [J].
Chang, Zhibo .
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2019, 18 (02) :1189-1195
[6]   Circular RNA expression profiling identifies hsa_circ_0011460 as a novel molecule in severe preeclampsia [J].
Deng, Na ;
Lei, Di ;
Huang, Jinfa ;
Yang, Zhuanhong ;
Fan, Cuifang ;
Wang, Suqing .
PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH, 2019, 17 :216-225
[7]   Downregulation of microRNA-1246 inhibits tumor growth and promotes apoptosis of cervical cancer cells by targeting thrombospondin-2 [J].
Du, Ping ;
Lai, Yue-Hua ;
Yao, De-Sheng ;
Chen, Jun-Ying ;
Ding, Nan .
ONCOLOGY LETTERS, 2019, 18 (03) :2491-2499
[8]   The role of thrombospondin-1 in apoptosis [J].
Friedl, P ;
Vischer, P ;
Freyberg, MA .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2002, 59 (08) :1347-1357
[9]   Functional significance of aberrantly expressed microRNAs in prostate cancer [J].
Goto, Yusuke ;
Kurozumi, Akira ;
Enokida, Hideki ;
Ichikawa, Tomohiko ;
Seki, Naohiko .
INTERNATIONAL JOURNAL OF UROLOGY, 2015, 22 (03) :242-252
[10]   Circular RNAs in Muscle Function and Disease [J].
Greco, Simona ;
Cardinali, Beatrice ;
Falcone, Germana ;
Martelli, Fabio .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (11)