circRAPGEF5 Contributes to Papillary Thyroid Proliferation and Metastatis by Regulation miR-198/FGFR1

被引：69

作者：

Liu, Weiwei ^{[1
]}

Zhao, Ji ^{[1
]}

Jin, Mingming ^{[1
]}

Zhou, Ming ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Dept Gen Surg, 1111 Xianxia Rd, Shanghai 200336, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2019年 / 14卷

关键词：

GASTRIC-CANCER; CIRCULAR RNA; MIGRATION; INVASION; EXPRESSION; CARCINOMA; MICRORNAS; CELLS;

D O I：

10.1016/j.omtn.2019.01.003

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The circular RNA RAPGEF5 (circRAPGEF5) is generated from five exons of the RAPGEF5 gene and abnormal expression in papillary thyroid cancer (PTC). However, whether circRAPGEF5 plays a role in PTC tumorigenesis remains unclear. The aim of the present study was to investigate the role of circRAPGEF5 in PTC. The results showed that circRAPGEF5 was upregulated in PTC tissues and cell lines. circRAPGEF5 knockdown inhibited cell proliferation, migration, and invasion in vitro; and circRAPGEF5 silencing downregulated fibroblast growth factor receptor 1 (FGFR1) expression by "sponging" miR-198, suppressing the aggressive biological behaviors of PTC. Luciferase reporter assays confirmed that circRAPGEF5 interacted with miR-198 and that miR-198 interacted with the 3' UTR of FGFR1 to downregulate its expression. Xenograft experiments confirmed that circRAPGEF5 knockdown suppressed FGFR1-mediated tumor growth by promoting miR-198 expression. circRAPGEF5 acts as a tumor promoter via a novel circRAPGEF5/miR-198/FGFR1 axis, providing a potential biomarker and therapeutic target for the management of PTC.

引用

页码：609 / 616

页数：8

共 33 条

[1] Integrated Genomic Characterization of Papillary Thyroid Carcinoma [J].

Agrawal, Nishant ;

Akbani, Rehan ;

Aksoy, B. Arman ;

Ally, Adrian ;

Arachchi, Harindra ;

Asa, Sylvia L. ;

Auman, J. Todd ;

Balasundaram, Miruna ;

Balu, Saianand ;

Baylin, Stephen B. ;

Behera, Madhusmita ;

Bernard, Brady ;

Beroukhim, Rameen ;

Bishop, Justin A. ;

Black, Aaron D. ;

Bodenheimer, Tom ;

Boice, Lori ;

Bootwalla, Moiz S. ;

Bowen, Jay ;

Bowlby, Reanne ;

Bristow, Christopher A. ;

Brookens, Robin ;

Brooks, Denise ;

Bryant, Robert ;

Buda, Elizabeth ;

Butterfield, Yaron S. N. ;

Carling, Tobias ;

Carlsen, Rebecca ;

Carter, Scott L. ;

Carty, Sally E. ;

Chan, Timothy A. ;

Chen, Amy Y. ;

Cherniack, Andrew D. ;

Cheung, Dorothy ;

Chin, Lynda ;

Cho, Juok ;

Chu, Andy ;

Chuah, Eric ;

Cibulskis, Kristian ;

Ciriello, Giovanni ;

Clarke, Amanda ;

Clayman, Gary L. ;

Cope, Leslie ;

Copland, John A. ;

Covington, Kyle ;

Danilova, Ludmila ;

Davidsen, Tanja ;

Demchok, John A. ;

DiCara, Daniel ;

Dhalla, Noreen .

CELL, 2014, 159 (03) :676-690

[2]

[Anonymous], 2018, JOULE

[3] RAS-MAPK Reactivation Facilitates Acquired Resistance in FGFR1-Amplified Lung Cancer and Underlies a Rationale for Upfront FGFR-MEK Blockade [J].

Bockorny, Bruno ;

Rusan, Maria ;

Chen, Wankun ;

Liao, Rachel G. ;

Li, Yvonne ;

Piccioni, Federica ;

Wang, Jun ;

Tan, Li ;

Thorner, Aaron R. ;

Li, Tianxia ;

Zhang, Yanxi ;

Miao, Changhong ;

Ovesen, Therese ;

Shapiro, Geoffrey I. ;

Kwiatkowski, David J. ;

Gray, Nathanael S. ;

Meyerson, Matthew ;

Hammerman, Peter S. ;

Bass, Adam J. .

MOLECULAR CANCER THERAPEUTICS, 2018, 17 (07) :1526-1539

[4] Thyroid cancer [J].

Cabanillas, Maria E. ;

McFadden, David G. ;

Durante, Cosimo .

LANCET, 2016, 388 (10061) :2783-2795

[5]

Cai HJ, 2018, AM J TRANSL RES, V10, P1690

[6] MicroRNAs in Cancer [J].

Di Leva, Gianpiero ;

Garofalo, Michela ;

Croce, Carlo M. .

ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 9, 2014, 9 :287-314

[7] Circular RNAs in Cancer - Lessons Learned From microRNAs [J].

Dragomir, Mihnea ;

Calin, George A. .

FRONTIERS IN ONCOLOGY, 2018, 8

[8] Effect of alkylglycerone phosphate synthase on the expression profile of circRNAs in the human thyroid cancer cell line FRO [J].

Hou, Shasha ;

Tan, Jian ;

Yang, Bing ;

He, Lu ;

Zhu, Yu .

ONCOLOGY LETTERS, 2018, 15 (05) :7889-7899

[9] miR-198 functions as a tumor suppressor in breast cancer by targeting CUB domain-containing protein 1 [J].

Hu, Yingbin ;

Tang, Ziyuan ;

Jiang, Bonian ;

Chen, Juying ;

Fu, Zhongpin .

ONCOLOGY LETTERS, 2017, 13 (03) :1753-1760

[10] Detecting and characterizing circular RNAs [J].

Jeck, William R. ;

Sharpless, Norman E. .

NATURE BIOTECHNOLOGY, 2014, 32 (05) :453-461

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