PMID- 35817112 OWN - NLM STAT- MEDLINE DCOM- 20220908 LR - 20220914 IS - 1879-1026 (Electronic) IS - 0048-9697 (Linking) VI - 845 DP - 2022 Nov 1 TI - The effects of endosulfan on cell migration and invasion in prostate cancer cells via the KCNQ1OT1/miR-137-3p/PTP4A3 axis. PG - 157252 LID - S0048-9697(22)04350-9 [pii] LID - 10.1016/j.scitotenv.2022.157252 [doi] AB - Endosulfan belongs to persistent organic pollutants (POPs), closely related to an increased risk of prostate cancer (PCa). The existing evidence shows that lncRNAs compete with miRNAs for binding sites and contribute to the onset and progression of human malignancies. In this study we investigate how endosulfan promotes cell migration and invasion in DU145 and PC3 prostate cancer cells through epigenetic mechanism of lncRNA-miRNA regulation. Based on our past research we focused on PTP4A3 and constructed wild-type (WT) and mutant PTP4A3 plasmids for further analysis. Our results revealed that transfection of PTP4A3-WT can lead to changes in the expression of epithelial-mesenchymal transition (EMT) biomarkers and critical proteins in the TGF-beta signaling pathway, and promote cell migration and invasion in PCa cells. Bioinformatics analysis shows that there were complementary sequences in PTP4A3 3'-UTR and KCNQ1OT1 3'-UTR to the seed sequence of hsa-miR-137-3p, and dual luciferase reporter assay indicates the potential binding capacity of miR-137-3p to 3'-UTR of PTP4A3 and KCNQ1OT1. We found that miR-137-3p mimic inhibited cell migration and invasion, as well as repressed alterations of EMT biomarkers and critical proteins in the TGF-beta signaling pathway. Rescue experiment results revealed that co-transfection of miR-137-3p mimic and PTP4A3-WT plasmid reversed these changes following transfection with miR-137-3p mimic alone. We found that KCNQ1OT1 was predominantly distributed in the cytoplasm from a subcellular fractionation assay. Functionally, silencing of KCNQ1OT1 repressed cell migration and invasion, and caused alterations of EMT biomarkers and critical proteins in the TGF-beta signaling pathway, which were all restored by co-transfection with anti-miR-137-3p or PTP4A3-WT plasmid. Furthermore, overexpression of miR-137-3p or silencing of KCNQ1OT1 dramatically rescued the effects of endosulfan on promoting cell migration and invasion. These findings suggest that endosulfan can indeed promote cell migration and invasion via the KCNQ1OT1/miR-137-3p/PTP4A3 axis in PCa cells. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Wang, Yue AU - Wang Y AD - Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. FAU - Guo, Yubing AU - Guo Y AD - Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. FAU - Lu, Yanyuan AU - Lu Y AD - Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. FAU - Sun, Yeqing AU - Sun Y AD - Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. FAU - Xu, Dan AU - Xu D AD - Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: jotan1995@163.com. LA - eng PT - Journal Article DEP - 20220708 PL - Netherlands TA - Sci Total Environ JT - The Science of the total environment JID - 0330500 RN - 0 (KCNQ1OT1 long non-coding RNA, human) RN - 0 (MIRN137 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Neoplasm Proteins) RN - 0 (Potassium Channels, Voltage-Gated) RN - 0 (RNA, Long Noncoding) RN - 0 (Transforming Growth Factor beta) RN - EC 3.1.3.48 (PTP4A3 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) RN - OKA6A6ZD4K (Endosulfan) SB - IM MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Endosulfan/toxicity MH - Humans MH - Male MH - *MicroRNAs/genetics MH - Neoplasm Proteins/genetics MH - Potassium Channels, Voltage-Gated MH - *Prostatic Neoplasms MH - *Protein Tyrosine Phosphatases/genetics MH - *RNA, Long Noncoding/genetics MH - Transforming Growth Factor beta/metabolism OTO - NOTNLM OT - Endosulfan OT - Invasion OT - KCNQ1OT1 OT - Migration OT - PTP4A3 OT - miR-137-3p COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/07/12 06:00 MHDA- 2022/09/09 06:00 CRDT- 2022/07/11 19:23 PHST- 2022/03/26 00:00 [received] PHST- 2022/07/03 00:00 [revised] PHST- 2022/07/05 00:00 [accepted] PHST- 2022/07/12 06:00 [pubmed] PHST- 2022/09/09 06:00 [medline] PHST- 2022/07/11 19:23 [entrez] AID - S0048-9697(22)04350-9 [pii] AID - 10.1016/j.scitotenv.2022.157252 [doi] PST - ppublish SO - Sci Total Environ. 2022 Nov 1;845:157252. doi: 10.1016/j.scitotenv.2022.157252. Epub 2022 Jul 8.