PMID- 34158077 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20220531 IS - 1477-7819 (Electronic) IS - 1477-7819 (Linking) VI - 19 IP - 1 DP - 2021 Jun 22 TI - CircLRP6 contributes to prostate cancer growth and metastasis by binding to miR-330-5p to up-regulate NRBP1. PG - 184 LID - 10.1186/s12957-021-02287-2 [doi] LID - 184 AB - BACKGROUND: Circular RNA low-density lipoprotein receptor-related protein 6 (circLRP6) is considered as an oncogene in many types of cancers. However, the function and mechanisms of circLRP6 in prostate cancer (PCa) tumorigenesis remain largely undefined. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were conducted to assess the expression of circLRP6, microRNA (miR)-330-5p, and nuclear receptor binding protein 1 (NRBP1). Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EDU) incorporation, flow cytometry, transwell, wound healing, and western blot assays were performed to detect cell proliferation, apoptosis, and metastasis in vitro. Subcutaneous tumor growth was observed in nude mice to investigate the role of circLRP6 in vivo. The targeting relationship between miR-330-5p and NRBP1 or circLRP6 was verified using dual-luciferase reporter, pull-down, and RNA immunoprecipitation (RIP) assays. Immunohistochemistry was employed to test relative protein expression. RESULTS: CircLRP6 was highly expressed in PCa tissues and cells, knockdown of circLRP6 impaired PCa cell growth and metastasis in vitro by affecting cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT). Mechanistic studies showed that circLRP6 could competitively bind with miR-330-5p to prevent the degradation of its target gene NRBP1. Rescue assay suggested that miR-330-5p inhibition reversed the inhibitory effects of circLRP6 knockdown on PCa cell growth and metastasis. Moreover, overexpression of miR-330-5p suppressed PCa progression via NRBP1. Notably, tumor formation assay indicated that circLRP6 silencing impeded tumor growth and EMT in vivo. CONCLUSION: Our findings demonstrated that circLRP6 promoted PCa tumorigenesis and metastasis through miR-330-5p/NRBP1 axis, suggesting a potential therapeutic target for PCa. FAU - Qin, Linghui AU - Qin L AD - Department of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangyang, 441021, Hubei, China. FAU - Sun, Xiaosong AU - Sun X AD - Department of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangyang, 441021, Hubei, China. FAU - Zhou, Fei AU - Zhou F AD - Department of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangyang, 441021, Hubei, China. FAU - Liu, Cheng AU - Liu C AD - Department of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangyang, 441021, Hubei, China. ivncdd@163.com. LA - eng PT - Journal Article DEP - 20210622 PL - England TA - World J Surg Oncol JT - World journal of surgical oncology JID - 101170544 RN - 0 (MIRN330 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NRBP1 protein, human) RN - 0 (RNA, Circular) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Vesicular Transport Proteins) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cell Movement MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Male MH - Mice MH - Mice, Nude MH - *MicroRNAs/genetics MH - Prognosis MH - *Prostatic Neoplasms/genetics MH - RNA, Circular/*genetics MH - *Receptors, Cytoplasmic and Nuclear/genetics MH - *Vesicular Transport Proteins/genetics PMC - PMC8220703 OTO - NOTNLM OT - Growth OT - Metastasis OT - MiR-330-5p OT - NRBP1 OT - Prostate cancer OT - circLRP6 COIS- The authors declare that they have no competing interests. EDAT- 2021/06/24 06:00 MHDA- 2021/06/25 06:00 PMCR- 2021/06/22 CRDT- 2021/06/23 05:46 PHST- 2021/04/13 00:00 [received] PHST- 2021/06/04 00:00 [accepted] PHST- 2021/06/23 05:46 [entrez] PHST- 2021/06/24 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2021/06/22 00:00 [pmc-release] AID - 10.1186/s12957-021-02287-2 [pii] AID - 2287 [pii] AID - 10.1186/s12957-021-02287-2 [doi] PST - epublish SO - World J Surg Oncol. 2021 Jun 22;19(1):184. doi: 10.1186/s12957-021-02287-2.