PMID- 30940151 OWN - NLM STAT- MEDLINE DCOM- 20190819 LR - 20200309 IS - 1476-4598 (Electronic) IS - 1476-4598 (Linking) VI - 18 IP - 1 DP - 2019 Apr 2 TI - Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression. PG - 73 LID - 10.1186/s12943-019-1007-1 [doi] LID - 73 AB - BACKGROUND: As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. However, little is known about the role of circTADA2A, also named hsa_circ_0043278, in osteosarcoma (OS). METHODS: CircTADA2A was selected from a previously reported circRNA microarray comparing OS cell lines and normal bone cells. QRT-PCR was used to detect the expression of circTADA2A in OS tissue and cell lines. Luciferase reporter, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to confirm the binding of circTADA2A with miR-203a-3p. OS cells were stably transfected with lentiviruses, and Transwell migration, Matrigel invasion, colony formation, proliferation, apoptosis, Western blotting, and in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circTADA2A, miR-203a-3p and CREB3. RESULTS: Our findings demonstrated that circTADA2A was highly expressed in both OS tissue and cell lines, and circTADA2A inhibition attenuated the migration, invasion and proliferation of OS cells in vitro as well as tumorigenesis and metastasis in vivo. A mechanistic study revealed that circTADA2A could readily sponge miR-203a-3p to upregulate the expression of CREB3, which was identified as a driver gene in OS. Furthermore, miR-203a-3p inhibition or CREB3 overexpression could reverse the circTADA2A silencing-induced impairment of malignant tumor behavior. CONCLUSIONS: CircTADA2A functions as a tumor promoter in OS to increase malignant tumor behavior through the miR-203a-3p/CREB3 axis, which could be a novel target for OS therapy. FAU - Wu, Yizheng AU - Wu Y AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. FAU - Xie, Ziang AU - Xie Z AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. FAU - Chen, Junxin AU - Chen J AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. FAU - Chen, Jiaxin AU - Chen J AD - Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China. FAU - Ni, Weiyu AU - Ni W AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. FAU - Ma, Yan AU - Ma Y AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. FAU - Huang, Kangmao AU - Huang K AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. FAU - Wang, Gangliang AU - Wang G AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. FAU - Wang, Jiying AU - Wang J AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. FAU - Ma, Jianjun AU - Ma J AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. FAU - Shen, Shuying AU - Shen S AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. 11207057@zju.edu.cn. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. 11207057@zju.edu.cn. FAU - Fan, Shunwu AU - Fan S AD - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. 0099203@zju.edu.cn. AD - Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang province, Hangzhou, 310016, Zhejiang Province, China. 0099203@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190402 PL - England TA - Mol Cancer JT - Molecular cancer JID - 101147698 RN - 0 (CREB3 protein, human) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (MIRN203 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 63231-63-0 (RNA) MH - Animals MH - Bone Neoplasms/genetics/*pathology MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Cyclic AMP Response Element-Binding Protein/*genetics MH - Cytoplasm/genetics MH - Disease Progression MH - Gene Expression Regulation, Neoplastic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Mice MH - MicroRNAs/*genetics MH - Neoplasm Metastasis MH - Neoplasm Transplantation MH - Osteosarcoma/genetics/*pathology MH - RNA/*genetics MH - RNA, Circular MH - Up-Regulation PMC - PMC6444890 OTO - NOTNLM OT - CREB3 OT - Metastasis OT - Osteosarcoma OT - circTADA2A OT - miR-203a-3p COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The present study was approved by the Hospital's Protection of Human Subjects Committee. CONSENT FOR PUBLICATION: All authors have agreed to publish this manuscript. COMPETING INTERESTS: The authors have no commercial or other associations that might pose a competing of interest. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/04/04 06:00 MHDA- 2019/08/20 06:00 PMCR- 2019/04/02 CRDT- 2019/04/04 06:00 PHST- 2018/12/04 00:00 [received] PHST- 2019/03/19 00:00 [accepted] PHST- 2019/04/04 06:00 [entrez] PHST- 2019/04/04 06:00 [pubmed] PHST- 2019/08/20 06:00 [medline] PHST- 2019/04/02 00:00 [pmc-release] AID - 10.1186/s12943-019-1007-1 [pii] AID - 1007 [pii] AID - 10.1186/s12943-019-1007-1 [doi] PST - epublish SO - Mol Cancer. 2019 Apr 2;18(1):73. doi: 10.1186/s12943-019-1007-1.