The novel circCLK3/miR-320a/FoxM1 axis promotes cervical cancer progression

被引:81
作者
Hong, Hanqing [1 ,2 ]
Zhu, Hai [1 ]
Zhao, Shujun [1 ]
Wang, Kaili [1 ]
Zhang, Nan [1 ]
Tian, Yun [1 ]
Li, Yan [1 ]
Wang, Yaping [1 ]
Lv, Xiaofeng [1 ]
Wei, Tianxiang [1 ]
Liu, Yan [1 ]
Fan, Suzhen [1 ]
Liu, Yang [3 ]
Li, Yuan [4 ]
Cai, Aojie [5 ]
Jin, Shuo [4 ]
Qin, Qiaohong [1 ,2 ]
Li, Hongyu [1 ,2 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Key Lab Gynecol Oncol, Zhengzhou 450052, Henan, Peoples R China
[3] Zhengzhou Univ, Dept Med Genet & Cell Biol, Sch Basic Med Sci, Zhengzhou 450052, Henan, Peoples R China
[4] Zhengzhou Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Zhengzhou 450052, Henan, Peoples R China
[5] Zhengzhou Univ, Affiliated Hosp 1, Genet & Prenatal Diag Ctr, Zhengzhou 450052, Henan, Peoples R China
关键词
CIRCULAR RNA; CELL-PROLIFERATION; EXPRESSION; GROWTH; FOXM1; TRANSCRIPTION; APOPTOSIS;
D O I
10.1038/s41419-019-2183-z
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
As a new class of non-coding RNA, circular RNAs (circRNAs) play crucial roles in the development and progression of various cancers. However, the detailed functions of circRNAs in cervical cancer have seldom been reported. In this study, circRNA sequence was applied to detect the differentially expressed circRNAs between cervical cancer tissues and adjacent normal tissues. The relationships between circCLK3 level with clinicopathological characteristics and prognosis were analyzed. In vitro CCK-8, cell count, cell colony, cell wound healing, transwell migration and invasion, and in vivo tumorigenesis and lung metastasis models were performed to evaluate the functions of circCLK3. The pulldown, RNA immunoprecipitation (RIP), luciferase reporter and rescue assays were employed to clarify the interaction between circCLK3 and miR-320a and the regulation of miR-320a on FoxM1. We found that the level of circCLK3 was remarkably higher in cervical cancer tissues than in adjacent normal tissues, and closely associated with tumor differentiation, FIGO stage and depth of stromal invasion. Down-regulated circCLK3 evidently inhibited cell growth and metastasis of cervical cancer in vitro and in vivo, while up-regulated circCLK3 significantly promoted cell growth and metastasis in vitro and in vivo. The pull-down, luciferase reporter and RIP assays demonstrated that circCLK3 directly bound to and sponge miR-320a. MiR-320a suppressed the expression of FoxM1 through directly binding to 3' UTR of FoxM1 mRNA. In addition, FoxM1 promoted cell proliferation, migration, and invasion of cervical cancer, while miR-320a suppressed cell proliferation, migration, and invasion through suppressing FoxM1, and circCLK3 enhanced cell proliferation, migration and invasion through sponging miR-320a and promoting FoxM1 expression. In summary, circCLK3 may serve as a novel diagnostic biomarker for disease progression and a promising molecular target for early diagnoses and treatments of cervical cancer.
引用
收藏
页数:19
相关论文
共 50 条
[41]   circ_0001006 Promotes Immune Escape in Non-small Cell Lung Cancer by Regulating the miR-320a/PD-L1 Axis [J].
Geng, Zhenying ;
Zhang, Guoqing .
IRANIAN JOURNAL OF IMMUNOLOGY, 2025, 22 (01)
[42]   Circular PVT1 regulates cell proliferation and invasion via miR-149-5p/FOXM1 axis in ovarian cancer [J].
Li, Min ;
Chi, Chi ;
Zhou, Liqin ;
Chen, Youguo ;
Tang, Xiuwu .
JOURNAL OF CANCER, 2021, 12 (02) :611-621
[43]   Long Noncoding RNA DLX6-AS1 Promotes the Progression in Cervical Cancer by Targeting miR-16-5p/ARPP19 Axis [J].
Xie, Fangfang ;
Xie, Guifang ;
Sun, Qian .
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS, 2020, 35 (02) :129-136
[44]   YTHDF1 promotes breast cancer progression by facilitating FOXM1 translation in an m6A-dependent manner [J].
Chen, Hengyu ;
Yu, Yuanhang ;
Yang, Ming ;
Huang, Haohao ;
Ma, Shenghui ;
Hu, Jin ;
Xi, Zihan ;
Guo, Hui ;
Yao, Guojie ;
Yang, Liu ;
Huang, Xiaoqing ;
Zhang, Feng ;
Tan, Guanghong ;
Wu, Huangfu ;
Zheng, Wuping ;
Li, Lei .
CELL AND BIOSCIENCE, 2022, 12 (01)
[45]   Circ_0000228 Promotes Cervical Cancer Progression via Regulating miR-337-3p/TGFBR1 Axis [J].
Xu, Yongqian ;
Dong, Xiaona ;
Ma, Baoli ;
Mu, Pingping ;
Kong, Xiang ;
Li, Dongmei .
CELL JOURNAL, 2022, 24 (02) :91-98
[46]   HLA-F-AS1/miR-330-3p/PFN1 axis promotes colorectal cancer progression [J].
Huang, Yongguo ;
Sun, Hong ;
Ma, Xiang ;
Zeng, Ye ;
Pan, Yang ;
Yu, Dongyang ;
Liu, Zhisheng ;
Xiang, Yun .
LIFE SCIENCES, 2020, 254
[47]   Long non-coding RNA SUMO1P3 promotes hepatocellular carcinoma progression through activating Wnt/β-catenin signalling pathway by targeting miR-320a [J].
Wu, Songsong ;
Chen, Sheng ;
Lin, Ning ;
Yang, Jianchuan .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2020, 24 (05) :3108-3116
[48]   FOXM1 as a prognostic biomarker promotes endometrial cancer progression via transactivation of SLC27A2 expression [J].
Feng, Yichen ;
Li, Shaojing ;
Zhang, Rong ;
Liu, Fei ;
Xu, Qinyang ;
Ding, Hongmei ;
Teng, Yincheng .
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY, 2018, 11 (08) :3846-3857
[49]   Splicing Factor DDX23, Transcriptionally Activated by E2F1, Promotes Ovarian Cancer Progression by Regulating FOXM1 [J].
Zhao, Chen ;
Li, Yingwei ;
Qiu, Chunping ;
Chen, Jingying ;
Wu, Huan ;
Wang, Qiuman ;
Ma, Xinyue ;
Song, Kun ;
Kong, Beihua .
FRONTIERS IN ONCOLOGY, 2021, 11
[50]   Kinesin family member 23, regulated by FOXM1, promotes triple negative breast cancer progression via activating Wnt/β-catenin pathway [J].
Li, Zhi ;
Yang, Hai-Yan ;
Zhang, Xiao-Lan ;
Zhang, Xu ;
Huang, Yu-Zhou ;
Dai, Xin-Yuan ;
Shi, Liang ;
Zhou, Guo-Ren ;
Wei, Ji-Fu ;
Ding, Qiang .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2022, 41 (01)