PMID- 33407514 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210111 IS - 1475-2867 (Print) IS - 1475-2867 (Electronic) IS - 1475-2867 (Linking) VI - 21 IP - 1 DP - 2021 Jan 6 TI - Circ-CCDC66 upregulates REXO1 expression to aggravate cervical cancer progression via restraining miR-452-5p. PG - 20 LID - 10.1186/s12935-020-01732-8 [doi] LID - 20 AB - BACKGROUND: Cervical cancer is one most common cancer types among females over the world. While its underlying mechanisms remain unclear. Circ-CCDC66 has been revealed to participate in multiple biological functions, and contribute to various diseases' progression. In the current study, we aimed to demonstrate the role of circ-CCDC66 in cervical cancer progression. METHODS: Real-time quantitative PCR (RT-qPCR) was conducted to measure the expression of circ-CCDC66, miR-452-5p, and REXO1 mRNA. Cell fractionation assay and RNA fluorescence in situ hybridization (FISH) were performed to locate circ-CCDC66 in cells. Cell account kit 8 (CCK-8) was used to detect cell proliferation ability. Transwell assay was applied to evaluate cell migration or invasion ability. Bioinformatics analysis, biotinylated RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assays were conducted to assess the association between miR-452 and circ-CCDC66 or REXO1. Western blot was applied to measure the protein expression of REXO1. The animal tumor model was used to assess the effect of circ-CCDC66 in vivo. RESULTS: The expression of circ-CCDC66 was upregulated in cervical cancer tumor tissues in comparison with normal tissues, and correlated with later tumor stage and larger tumor size. Downregulated circ-CCDC66 inhibited cervical cancer cell proliferation, migration, and invasion. Circ-CCDC66 was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. MiR-452-5p directly targeted to REXO1. Circ-CCDC66 regulated REXO1 expression to modulate cervical cancer progression via miR-452-5p. Moreover, downregulated circ-CCDC66 was found to suppress tumor growth in vivo. CONCLUSION: Our results demonstrated the role of circ-CCDC66/miR-452-5p/REXO1 axis in cervical cancer progression, we might provide novel therapeutic targets for cervical cancer clinical intervention. FAU - Zhang, Yan AU - Zhang Y AUID- ORCID: 0000-0001-7798-531X AD - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China. Doctor8118@163.com. FAU - Li, Xing AU - Li X AD - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Zhang, Jun AU - Zhang J AD - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Mao, Lin AU - Mao L AD - Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China. LA - eng PT - Journal Article DEP - 20210106 PL - England TA - Cancer Cell Int JT - Cancer cell international JID - 101139795 PMC - PMC7789749 OTO - NOTNLM OT - Cervical cancer OT - Circ-CCDC66 OT - Circular RNA OT - REXO1 OT - miR-452-5p COIS- There is no conflict of interests to declare in the current study. EDAT- 2021/01/08 06:00 MHDA- 2021/01/08 06:01 PMCR- 2021/01/06 CRDT- 2021/01/07 05:47 PHST- 2020/08/26 00:00 [received] PHST- 2020/12/21 00:00 [accepted] PHST- 2021/01/07 05:47 [entrez] PHST- 2021/01/08 06:00 [pubmed] PHST- 2021/01/08 06:01 [medline] PHST- 2021/01/06 00:00 [pmc-release] AID - 10.1186/s12935-020-01732-8 [pii] AID - 1732 [pii] AID - 10.1186/s12935-020-01732-8 [doi] PST - epublish SO - Cancer Cell Int. 2021 Jan 6;21(1):20. doi: 10.1186/s12935-020-01732-8.