PMID- 32703944 OWN - NLM STAT- MEDLINE DCOM- 20210325 LR - 20210723 IS - 2041-4889 (Electronic) VI - 11 IP - 7 DP - 2020 Jul 23 TI - Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3. PG - 562 LID - 10.1038/s41419-020-02785-3 [doi] LID - 562 AB - Accumulating evidences indicate that circular RNAs (circRNAs), a subclass of noncoding RNAs, play important role in regulating gene expression in eukaryotes. Hsa_circ_0046263 (circ-0046263) was found aberrantly expressed in nasopharyngeal carcinoma (NPC), but its role in tumor growth and metastasis remains largely unclear. Sanger sequencing, RNase R assay, and nucleic acid electrophoresis were conducted to verify the identification of circ-0046263. Nuclear separation and fluorescence in situ hybridization (FISH) assays were used to determine the localization of circ-004263. Dual luciferase reporter and RNA immunoprecipitation (RIP) were employed to confirm the binding of circ-0046263 with miR-133a-5p. Colony formation, proliferation, wound healing, transwell, western blot, and in vivo tumor growth and metastasis assays were performed to assess the roles of circ-0046263, miR-133a-5p, IGFBP3 and their interactions in NPC cells. Circ-0046263 was upregulated in both NPC cell lines and tissues. The in vitro functional studies revealed that knockdown of circ-0046263 inhibited the proliferation, invasion, and migration of NPC cells, whereas its overexpression produced the opposite result. In vivo experiments indicated that knockdown or overexpression of circ-0046263 attenuated or promoted tumor growth and metastasis, respectively. Mechanistically, circ-0046263 could act as a miRNA sponge to absorb miR-133a-5p and upregulate the expression of miRNA downstream target IGFBP3. In addition, miR-133a-5p inhibition or IGFBP3 overexpression could rescue the malignant behavior induced by circ-0046263 silencing. Finally, circ-0046263 plays a tumor-promoting role in NPC to enhance malignant behavior through the miR-133a-5p/IGFBP3 axis, which could be a potential target for NPC therapy. FAU - Yin, Li AU - Yin L AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. FAU - Chen, Jie AU - Chen J AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. AD - Xuzhou Medical University, Xuzhou, Jiangsu, China. FAU - Ma, Chengxian AU - Ma C AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. FAU - Pei, Shuai AU - Pei S AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. AD - Xuzhou Medical University, Xuzhou, Jiangsu, China. FAU - Du, Mingyu AU - Du M AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. FAU - Zhang, Yufeng AU - Zhang Y AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. FAU - Feng, Yong AU - Feng Y AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. FAU - Yin, Rong AU - Yin R AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. FAU - Bian, Xiuhua AU - Bian X AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. FAU - He, Xia AU - He X AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. hexiabm@163.com. AD - Xuzhou Medical University, Xuzhou, Jiangsu, China. hexiabm@163.com. FAU - Feng, Jifeng AU - Feng J AUID- ORCID: 0000-0002-7979-2391 AD - The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China. jifeng_feng@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200723 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (IGFBP3 protein, human) RN - 0 (Insulin-Like Growth Factor Binding Protein 3) RN - 0 (MIRN133 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) SB - IM MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - *Disease Progression MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Gene Silencing MH - Humans MH - Insulin-Like Growth Factor Binding Protein 3/*genetics/metabolism MH - Male MH - MicroRNAs/genetics/metabolism MH - Middle Aged MH - Nasopharyngeal Carcinoma/*genetics/*pathology MH - Neoplasm Invasiveness MH - Neoplasm Metastasis MH - RNA, Circular/genetics/*metabolism MH - Up-Regulation/*genetics PMC - PMC7378203 COIS- The authors declare that they have no conflict of interest. EDAT- 2020/07/25 06:00 MHDA- 2021/03/26 06:00 PMCR- 2020/07/23 CRDT- 2020/07/25 06:00 PHST- 2020/02/25 00:00 [received] PHST- 2020/07/13 00:00 [accepted] PHST- 2020/07/08 00:00 [revised] PHST- 2020/07/25 06:00 [entrez] PHST- 2020/07/25 06:00 [pubmed] PHST- 2021/03/26 06:00 [medline] PHST- 2020/07/23 00:00 [pmc-release] AID - 10.1038/s41419-020-02785-3 [pii] AID - 2785 [pii] AID - 10.1038/s41419-020-02785-3 [doi] PST - epublish SO - Cell Death Dis. 2020 Jul 23;11(7):562. doi: 10.1038/s41419-020-02785-3.