MicroRNA-200c impairs uterine receptivity formation by targeting FUT4 and α1,3-fucosylation

Abstract

Successful embryo implantation requires the establishment of a receptive endometrium. Poor endometrial receptivity has generally been considered as a major cause of infertility. Protein glycosylation is associated with many physiological and pathological processes. The fucosylation is catalyzed by the specific fucosyltransferases. Fucosyltransferase IV (FUT4) is the key enzyme for the biosynthesis of α1,3-fucosylated glycans carried by glycoproteins, and the previous studies showed FUT4 expression changed dynamically during perimplantation. MicroRNAs (miRNAs) are known to regulate specific gene expression. However, the relationship between specific miRNA and FUT4, as well as the role of miRNA/FUT4 in the establishment of uterine receptivity remains elusive. In the current study, we reported that the levels of miR-200 family members were significantly increased in serum from infertility and abortion patients relative to healthy non-pregnancy and early-pregnancy women. Among these, miR-200c was the most sensitive diagnostic criterion for infertility by receiver operating characteristic curve analysis. FUT4 was lower in the serum from infertility and abortion patients compared with the healthy non-pregnancy and early-pregnancy women. Using endometrial cell lines and a mouse model, we demonstrated that miR-200c targeted and inhibited FUT4 expression, leading to the dysfunction of uterine receptivity. Our results also revealed that miR-200c decreased α1.3-fucosylation on glycoprotein CD44, which further inactivated Wnt/β-catenin signaling pathway. Taken together, miR-200c hampers uterine receptivity formation by targeting FUT4 and α1.3-fucosylation on CD44. miR-200c and FUT4 may be applied together as the potential markers for endometrial receptivity, and useful diagnostic and therapeutic targets for infertility.

Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/β-catenin axis

“…Many literatures have reported FUT family activated wnt/β-catenin pathway in a variety of biological processes 24 . In order to figure out the function of molecular mechanisms induced by HOTAIR, miR-17-5p and FUT2, we wondered FUT2 could exert its posttranslational modification function and participate in wnt/β-catenin pathway activation process.…”

Loss of CDYL Results in Suppression of CTNNB1 and Decreased Endometrial Receptivity

“…Using String and Cytospace online tools, genes in these clusters were mapped into an interaction network ( Figure 4E and Supplementary Figure S2). Strikingly, we found genes including catenin beta 1 (CTNNB1), NOTCH1 (notch receptor 1), and GJA1 (gap junction protein, alpha), which are well-known regulators of endometrial receptivity (Zhang et al, 2012;Van Sinderen et al, 2014;Winterhager and Kidder, 2015;Su et al, 2016;Yu et al, 2017;Zheng et al, 2017), centered in this network. In addition, transcripts of EPHA2 (EPH Receptor A2), IL6ST (Interleukin 6 Signal Transducer), JAG1 (Jagged canonical notch ligand 1), MSX1 (msh homeobox 1), PLA2G4A (phospholipase A2, group IVA), TGFB1 (transforming growth factor beta 1), SPHK1 (sphingosine kinase 1), and VANGL2 (VANGL planar cell polarity protein 2) exhibited > 1.5-fold change of expression (red dot), which have been proved functional in the endometrial receptivity regulation.…”

miR-200c /FUT4 axis prevents the migration, invasion and proliferation of colon cancer cells by downregulating Wnt/β-catenin pathway

“…Lovo and SW480 cells were divided into (1) blank control group (BC): no treatment; (2) miR-200c overexpression group: cells were transfected with 100 nM miR-200c mimic lentiviral vector; 17 (3) fucosyltransferase 4 (FUT4) silencing group (si-FUT4): cells were transfected with 50 nM FUT4 siRNA lentiviral vector; 17 (4) miR-200c + FUT4 overexpression negative control group (miR-200c + NC1): cells were transfected with 100 nM miR-200c overexpression lentiviral vector and 50 nM FUT4 overexpression negative control lentiviral vector; (5) miR-200c + FUT4 overexpression group (miR-200c + FUT4): cells were transfected with 100 nM miR-200c overexpression lentiviral vector and 50 nM FUT4 overexpression lentiviral vectors.…”