title: Let-7i-Induced Atg4B Suppression Is Essential for Autophagy of Placental Trophoblast in Preeclampsia.
abstract: Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc.
authors: State key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors: Yinyan
authors: Y
authors: Xu
authors: State key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors: Xinyan
authors: X
authors: Huang
authors: State key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors: Juan
authors: J
authors: Xie
authors: State key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors: Yanni
authors: Y
authors: Chen
authors: State key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors: Jing
authors: J
authors: Fu
authors: State key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors: Li
authors: L
authors: Wang
mesh_terms: D000328:Adult; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
chemical_list: D000071183:Autophagy-Related Proteins; C477012:MAP1LC3A protein, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; C487931:mirnlet7 microRNA, human; C507524:ATG4B protein, human; D003546:Cysteine Endopeptidases