PMID- 29048659 OWN - NLM STAT- MEDLINE DCOM- 20180702 LR - 20220331 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 38 IP - 5 DP - 2017 Nov TI - MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 to suppress the invasion and migration of breast cancer. PG - 3144-3152 LID - 10.3892/or.2017.5968 [doi] AB - Interleukin-8 (IL-8), which is secreted by cancer cells undergoing epithelial-mesenchymal transition (EMT), can promote EMT in adjacent epithelial-like cells. MicroRNAs (miRNAs/miRs) can affect the expression of target genes via binding to their 3'-untranslated regions (3'-UTRs), which may subsequently affect the biological behaviors of cancer cells. In our previous study, miR-520c-3p was predicted to directly target the 3'-UTR of IL-8. Therefore, the present study was carried out to investigate whether miR-520c-3p can interact with the IL-8 gene and regulate the EMT of breast cancer cells. Web-based prediction algorithms were used to identify miRNAs that potentially target the IL-8 transcript. Luciferase reporter assays were used to confirm the targeting of IL-8 by miR-520c-3p. Reverse transcription-quantitative PCR and western blot analyses were used to examine the levels of IL-8 and EMT-related genes in breast cancer cells. The functional impact of miR-520c-3p on EMT phenotype was evaluated using Transwell and wound-healing assays, and rescue experiments were conducted by overexpressing IL-8 to determine its effect on cell properties. miR-520c-3p was predicted by all three databases, which strongly suggested its interaction with the 3'-UTR of IL-8. The relative Renilla luciferase activity of luciferase reporter construct containing the wild-type 3'-UTR of IL-8 was markedly decreased by miR-520c-3p transfection when compared with scrambled miRNA control transfection (P<0.001). In addition, compared with the scrambled miRNA control transfection, the overexpression of miR-520c-3p significantly reduced the expression of IL-8, and resulted in increased E-cadherin and decreased vimentin and fibronectin levels in MCF-7 and T47D cells (all P<0.001). Introduction of miR-520c-3p inhibited the invasion and migration of MCF-7 and T47D cells (all P<0.001). By contrast, the rescue of IL-8 expression led to the recovery of EMT-related protein expression patterns and cell motility and invasion capabilities. In conclusion, aberrant miR-520c-3p expression may lead to reduced IL-8 expression and promote the mesenchymal phenotype in breast cancer cells, thereby increasing invasive growth. FAU - Tang, Cui-Ping AU - Tang CP AD - Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China. FAU - Zhou, Han-Jing AU - Zhou HJ AD - Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China. FAU - Qin, Jian AU - Qin J AD - Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China. FAU - Luo, Yi AU - Luo Y AD - Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China. FAU - Zhang, Tao AU - Zhang T AD - Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China. LA - eng PT - Journal Article DEP - 20170919 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (CXCL8 protein, human) RN - 0 (Interleukin-8) RN - 0 (MIRN520 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Breast Neoplasms/*genetics/pathology MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Epithelial-Mesenchymal Transition/genetics MH - Female MH - Gene Expression Regulation, Neoplastic/genetics MH - Humans MH - Interleukin-8/*genetics MH - MCF-7 Cells MH - MicroRNAs/*genetics MH - Neoplasm Invasiveness/*genetics/pathology MH - Signal Transduction/genetics EDAT- 2017/10/20 06:00 MHDA- 2018/07/03 06:00 CRDT- 2017/10/20 06:00 PHST- 2017/03/30 00:00 [received] PHST- 2017/08/25 00:00 [accepted] PHST- 2017/10/20 06:00 [pubmed] PHST- 2018/07/03 06:00 [medline] PHST- 2017/10/20 06:00 [entrez] AID - 10.3892/or.2017.5968 [doi] PST - ppublish SO - Oncol Rep. 2017 Nov;38(5):3144-3152. doi: 10.3892/or.2017.5968. Epub 2017 Sep 19.