Circular RNA circPPP6R3 upregulates CD44 to promote the progression of clear cell renal cell carcinoma via sponging miR-1238-3p

被引:16
作者
Chen, Zhiliang [1 ,2 ]
Zheng, Zaosong [3 ]
Xie, Yingwei [1 ,2 ]
Zhong, Qiyu [1 ,2 ]
Shangguan, Wentai [1 ,2 ]
Zhang, Yishan [1 ,2 ]
Zhu, Dingjun [1 ,2 ]
Xie, Wenlian [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Urol, Guangzhou 510120, Peoples R China
[2] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China
[3] Southern Med Univ, Nanfang Hosp, Dept Urol, Guangzhou 510515, Peoples R China
基金
中国国家自然科学基金;
关键词
PROLIFERATION; EXPRESSION; TUMORIGENICITY; TRANSCRIPTION; SURVIVAL; DATABASE; CIRCRNA;
D O I
10.1038/s41419-021-04462-5
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Circular RNAs (circRNAs) are a type of covalently closed circular-formed RNAs and play crucial roles in the oncogenesis and progression of various human cancers. Here we identified a novel circRNA, circPPP6R3, to be highly expressed both in clear cell renal cell carcinoma (ccRCC) tissues and cell lines based on analyzing high-throughput sequencing data and qRT-PCR analysis. Highly expressed circPPP6R3 was positively correlated with higher histological grade, T stage, and M stage as well as advanced clinical stage of ccRCC patients. Functionally, knockdown of circPPP6R3 attenuated the proliferation, migration, and invasion of ccRCC cells whereas overexpression had the reverse effects. Mechanistically, the biotin-labeled pull-down assay and dual-luciferase reporter assay revealed that circPPP6R3 directly interacted with miR-1238-3p. miR-1238-3p inhibitors had a rescue effect on the proliferative and metastatic capacities by knockdown of circPPP6R3. Moreover, RNA-sequencing analysis and dual-luciferase reporter assay indicated that circPPP6R3 upregulated CD44, a cell-surface glycoprotein contributed to the cell adhesion and metastasis, via sponging to miR-1238-3p. Further investigation revealed that MMP9 and Vimentin were regulated by CD44 in ccRCC. Our study thus provided evidence that the regulatory network involving circPPP6R3/miR-1238-3p/CD44 axis might provide promising biomarkers as well as a therapeutic approach for ccRCC.
引用
收藏
页数:12
相关论文
共 47 条
[1]   Predicting effective microRNA target sites in mammalian mRNAs [J].
Agarwal, Vikram ;
Bell, George W. ;
Nam, Jin-Wu ;
Bartel, David P. .
ELIFE, 2015, 4
[2]   Increased Expression of CD44s in Conventional Renal Cell Carcinomas with Renal Vein or Vena Cava Thrombosis [J].
Altinel, Mert ;
Arpali, Emre ;
Turhan, Nesrin ;
Gonenc, Faruk ;
Yazicioglu, Ahmet .
UROLOGIA INTERNATIONALIS, 2008, 81 (04) :452-455
[3]   Circular RNAs in Cancer [J].
Bach, Duc-Hiep ;
Lee, Sang Kook ;
Sood, Anil K. .
MOLECULAR THERAPY-NUCLEIC ACIDS, 2019, 16 :118-129
[4]   Renal cancer [J].
Capitanio, Umberto ;
Montorsi, Francesco .
LANCET, 2016, 387 (10021) :894-906
[5]   CD44 targets Wnt/β-catenin pathway to mediate the proliferation of K562 cells [J].
Chang, Guoqiang ;
Zhang, Hongju ;
Wang, Jian ;
Zhang, Yujuan ;
Xu, Hua ;
Wang, Chijuan ;
Zhang, Hairui ;
Ma, Li ;
Li, Qinghua ;
Pang, Tianxiang .
CANCER CELL INTERNATIONAL, 2013, 13
[6]   miRDB: an online database for prediction of functional microRNA targets [J].
Chen, Yuhao ;
Wang, Xiaowei .
NUCLEIC ACIDS RESEARCH, 2020, 48 (D1) :D127-D131
[7]   circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1 [J].
Cheng, Zhuoan ;
Yu, Chengtao ;
Cui, Shaohua ;
Wang, Hui ;
Jin, Haojie ;
Wang, Cun ;
Li, Botai ;
Qin, Meilin ;
Yang, Chen ;
He, Jia ;
Zuo, Qiaozhu ;
Wang, Siying ;
Liu, Jun ;
Ye, Weidong ;
Lv, Yuanyuan ;
Zhao, Fangyu ;
Yao, Ming ;
Jiang, Liyan ;
Qin, Wenxin .
NATURE COMMUNICATIONS, 2019, 10 (1)
[8]   Renal cell carcinoma recurrences and metastases in primary non-metastatic patients: a population-based study [J].
Dabestani, Saeed ;
Thorstenson, Andreas ;
Lindblad, Per ;
Harmenberg, Ulrika ;
Ljungberg, Borje ;
Lundstam, Sven .
WORLD JOURNAL OF UROLOGY, 2016, 34 (08) :1081-1086
[9]   Identifying and Characterizing circRNA-Protein Interaction [J].
Du, William W. ;
Zhang, Chao ;
Yang, Weining ;
Yong, Tianqiao ;
Awan, Faryal Mehwish ;
Yang, Burton B. .
THERANOSTICS, 2017, 7 (17) :4183-4191
[10]   CircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs [J].
Dudekulay, Dawood B. ;
Panda, Amaresh C. ;
Grammatikakis, Ioannis ;
De, Supriyo ;
Abdelmohsen, Kotb ;
Gorospe, Myriam .
RNA BIOLOGY, 2016, 13 (01) :34-42