PMID- 29512715 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20181114 IS - 1791-244X (Electronic) IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 41 IP - 6 DP - 2018 Jun TI - miR‑377 targets CUL4A and regulates metastatic capability in ovarian cancer. PG - 3147-3156 LID - 10.3892/ijmm.2018.3540 [doi] AB - The incidence and recurrence rates of ovarian cancer are still high, and once the disease metastasizes, it is nearly always fatal. Cullin 4A (CUL4A) serves a significant role in tumourigenesis and tumour progression; however, the effect and mechanisms underlying CUL4A overexpression are still unknown. The role of microRNAs (miRs) in the regulation of metastatic capability in ovarian cancer cell lines was investigated. The interaction between miR‑377 and CUL4A was investigated using bioinformatics analyses and dual‑luciferase reporter assays. Furthermore, miR‑377 mRNA and protein levels were detected using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively and cell migration and invasion were detected using a Transwell assay. Results revealed that CUL4A expression was negatively associated with miR‑377 levels in ovarian cancer tissues and cell lines. Through in silico analysis, the targeting effect of miR‑377 on CUL4A was verified. Ectopic expression of miR‑377 in SKOV3 cells downregulated the level of CUL4A, and significantly reduced the migratory ability of the cells. miR‑377 overexpression led to reduced activity of the Wnt/beta‑catenin signaling pathway, and regulated the expression of matrix metalloproteinase‑2, and 9, and epithelial‑mesenchymal transition (EMT)‑associated protein. These results suggested that miR‑377 is a significant negative regulator of CUL4A that controls cancer cell progression in ovarian cancer cell lines. FAU - Yu, Rufen AU - Yu R AD - Department of Obstetrics and Gynecology, Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325200, P. R. China. FAU - Cai, Limei AU - Cai L AD - Department of Obstetrics and Gynecology, Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325200, P. R. China. FAU - Chi, Yingui AU - Chi Y AD - Department of Obstetrics and Gynecology, Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325200, P. R. China. FAU - Ding, Xiangcui AU - Ding X AD - Department of Obstetrics and Gynecology, Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325200, P. R. China. FAU - Wu, Xueqing AU - Wu X AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, The First Provincial Wenzhou Hospital of Zhejiang, Wenzhou, Zhejiang 325000, P. R. China. LA - eng PT - Journal Article DEP - 20180307 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (CUL4A protein, human) RN - 0 (Cullin Proteins) RN - 0 (MIRN377 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Cell Line, Tumor MH - Cell Transformation, Neoplastic/genetics/pathology MH - Cullin Proteins/genetics/*metabolism MH - Female MH - Gene Expression Regulation, Neoplastic/genetics/physiology MH - Humans MH - MicroRNAs/genetics/*metabolism MH - Neoplasm Metastasis/genetics/*physiopathology MH - Ovarian Neoplasms/genetics/*metabolism/pathology PMC - PMC5881808 EDAT- 2018/03/08 06:00 MHDA- 2018/09/11 06:00 PMCR- 2018/03/07 CRDT- 2018/03/08 06:00 PHST- 2017/05/17 00:00 [received] PHST- 2018/01/31 00:00 [accepted] PHST- 2018/03/08 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] PHST- 2018/03/08 06:00 [entrez] PHST- 2018/03/07 00:00 [pmc-release] AID - ijmm-41-06-3147 [pii] AID - 10.3892/ijmm.2018.3540 [doi] PST - ppublish SO - Int J Mol Med. 2018 Jun;41(6):3147-3156. doi: 10.3892/ijmm.2018.3540. Epub 2018 Mar 7.