PMID- 30081007 OWN - NLM STAT- MEDLINE DCOM- 20181003 LR - 20190816 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 209 DP - 2018 Sep 15 TI - Tumor necrosis factor-alpha suppresses the invasion of HTR-8/SVneo trophoblast cells through microRNA-145-5p-mediated downregulation of Cyr61. PG - 132-139 LID - S0024-3205(18)30451-X [pii] LID - 10.1016/j.lfs.2018.08.005 [doi] AB - Deficiency in trophoblast invasion is causally linked to the pathogenesis of preeclampsia. Tumor necrosis factor-alpha (TNF-alpha) shows the ability to suppress the invasiveness of trophoblasts, while cysteine-rich 61 (Cyr61) exerts an opposite function in trophoblast invasion. This study was designed to check the hypothesis that cysteine-rich 61 (Cyr61) may be involved in the anti-invasive activity of TNF-alpha in trophoblasts. To this end, we examined the effect of TNF-alpha treatment on Cyr61 expression in HTR-8/SVneo trophoblast cells and investigated the mechanism for the regulation of Cyr61 by TNF-alpha. Gain-of-function experiments were performed to clarify the role of Cyr61 in TNF-alpha-dependent suppression of trophoblast invasion. It was found that TNF-alpha at 1 and 10 ng/mL reduced Cyr61 protein levels by 30 and 80%, respectively, in HTR-8/SVneo cells, but did not affect the mRNA expression of Cyr61. Mechanistically, microRNA (miR)-145-5p was stimulated by TNF-alpha and negatively regulated the expression of Cyr61 via interaction with its 3'-untranslated region. Functionally, overexpression of miR-145-5p significantly impaired the migration and invasion of HTR-8/SVneo cells. Depletion of miR-145-5p rescued HTR-8/SVneo cells from TNF-alpha-mediated invasion suppression, which coincided with prevention of Cyr61 downregulation by TNF-alpha. In addition, overexpression of Cyr61 partially restored the invasion of HTR8/SVneo cells co-transfected with miR-145-5p mimic or exposed to TNF-alpha. Taken together, miR-145-5p-mediated downregulation of Cyr61 is required for the anti-invasive effect of TNF-alpha on trophoblasts. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Wen, Zhengfang AU - Wen Z AD - Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Departments of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China. FAU - Chen, Yue AU - Chen Y AD - Department of Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Long, Yu AU - Long Y AD - Department of Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. FAU - Yu, Jian AU - Yu J AD - Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Nanning, China. FAU - Li, Mujun AU - Li M AD - Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. Electronic address: wzf120@126.com. LA - eng PT - Journal Article DEP - 20180803 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (CCN1 protein, human) RN - 0 (Cysteine-Rich Protein 61) RN - 0 (MIRN145 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Cells, Cultured MH - Cysteine-Rich Protein 61/genetics/*metabolism MH - Gene Expression Regulation/*drug effects MH - Humans MH - MicroRNAs/*genetics MH - Trophoblasts/*drug effects/metabolism/pathology MH - Tumor Necrosis Factor-alpha/*pharmacology OTO - NOTNLM OT - Cyr61 OT - Invasion OT - Preeclampsia OT - TNF-alpha OT - microRNA EDAT- 2018/08/07 06:00 MHDA- 2018/10/04 06:00 CRDT- 2018/08/07 06:00 PHST- 2018/04/26 00:00 [received] PHST- 2018/07/26 00:00 [revised] PHST- 2018/08/02 00:00 [accepted] PHST- 2018/08/07 06:00 [pubmed] PHST- 2018/10/04 06:00 [medline] PHST- 2018/08/07 06:00 [entrez] AID - S0024-3205(18)30451-X [pii] AID - 10.1016/j.lfs.2018.08.005 [doi] PST - ppublish SO - Life Sci. 2018 Sep 15;209:132-139. doi: 10.1016/j.lfs.2018.08.005. Epub 2018 Aug 3.