The miR‚Ä?7a‚Ä?p/USP25 axis participates in the pathogenesis of recurrent miscarriage by inhibiting trophoblast migration and invasion
Authors: Yi Zhang
Jinli Ding
Tailang Yin
Shujie Liao
Yanxiang Cheng
Jing Yang
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: USP25; invasion; miRNA-27a-3p; migration; recurrent miscarriage
Affiliations: Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, China., Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China., Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China., Department of Obstetrics and Gynecology, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract:  Insufficient invasion ability of trophoblasts might be associated with the development of recurrent miscarriage (RM). Ubiquitin-specific protease 25 (USP25) can regulate the processes of invasion and migration in different types of cancer cells. However, the effect of USP25 on trophoblasts and its roles in the development of RM are unknown. In this study, we first analyzed the USP25 expression in placental villous tissues from RM patients, and then assessed the roles of USP25 in epithelial-to-mesenchymal transition (EMT), invasion and migration of trophoblasts. Furthermore, bioinformatics prediction and luciferase reporter assay were used to explore the mechanism of microRNA on USP25 expression, and regulation of USP25 expression in trophoblasts was assessed following transfection with microRNA mimics or inhibitor. The results showed that the expression of USP25 in the placental villous tissues was downregulated in RM patients. Knockdown of USP25 suppressed the EMT process, the invasion and migration capability of trophoblast cells, while overexpression of USP25 exhibited opposite results. Mechanistically, miR-27a-3p could regulate USP25 expression by binding to the 3'-untranslated region of USP25 in trophoblasts. Quantitative real-time polymerase chain reaction results found the expression of miR-27a-3p were negatively related to USP25 in RM patients. MiR-27a-3p mimics inhibited but miR-27a-3p inhibitor enhanced the migration and invasion capability of trophoblasts. Furthermore, sh-USP25 counteracted the promotion of invasion and migration mediated by the miR-27a-3p inhibitor. Taken together, these data indicate that USP25 downregulation by miR-27a-3p contributes to the EMT process, thereby inhibiting the migration and invasion of trophoblast cells, and these findings might provide potential biomarkers for RM. 

Retracted: No

PubPeer comments:
 This paper was recently corrected, even if it contained manipulated data.  , 
 #1 Dear Indigofera Tanganyikensis, thank you very much for pointing out the errors in our manuscript. Due to the problem of image preservation during the experiment, duplicate images were wrongly used in the drawing process. After the article was published, we discovered these errors and immediately contacted the editorial office to make a correction, the electronic publication of corrigendum was online in August 2020 (PMID: 33351276, DOI: 10.1002 jcp.30012). We are very sorry for our mistakes. In the future, we will certainly remember the lesson and carefully sort out the experimental data and images. Sincerely, Jinli Ding ,