Ezrin T567 phosphorylation regulates migration and invasion of ectopic endometrial stromal cells by changing actin cytoskeleton

Chen, Chaolu; Ye, Chaoshuang; Xia, Jianmei; Zhou, Yong; Wu, Renyi

doi:10.1016/j.lfs.2020.117681

Cited by 16 publications

(13 citation statements)

References 24 publications

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“…The purity of isolated endometrial stromal cells were determined by diffuse and strong cytoplasmic immunostaining for vimentin (marker of stromal cells) and weak cellular staining for cytokeratin 7 (marker of epithelial cells; Fig. 2A ) ( 28 ). To examine the possible role of miR-202 in primary ESCs from patients with ectopic endometriosis, the migratory and invasive capabilities were measured using Transwell and wound healing assays, respectively, following transfection with miR-202 mimics.…”

Section: Resultsmentioning

confidence: 99%

“…293T cells (ATCC) used for luciferase assays were cultured in DMEM (Gibco; Thermo Fisher Scientific, Inc.) supplemented with 10% FBS under 37°C in a humidified atmosphere under 5% CO 2 . Cellular purity was examined by immunofluorescence staining for strong cytoplasmic immunostaining for vimentin (marker of stromal cells) and negative cellular staining for cytokeratin 7 (markers of epithelial cells) ( 28 , 29 ).…”

Section: Methodsmentioning

confidence: 99%

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MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway

et al. 2020

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The enhanced migratory ability of endometrial stromal cells (ESCs) is a key factor in the formation of functional endometrium-like tissues outside the uterine cavity during endometriosis (EMS). Although accumulating evidence has suggested the importance of microRNAs (miRNAs) in the pathogenesis of EMS, the role of particular miRNAs in the invasiveness of ESCs remain poorly understood. In the present study, the function of miRNAs in the invasiveness of ESCs, along with the associated underlying mechanism involved, were investigated. Initially, the expression patterns of miRNAs in the ectopic and eutopic endometrium isolated from patients with EMS were analyzed using microarray. MicroRNA-202-5p (miR-202) was selected for further study due to its previously reported suppressive effects on the invasion in various types of cancers. The expression of miR-202 and K-Ras in eutopic and ectopic endometrioma tissues were detected using reverse transcription-quantitative PCR, immunohistochemistry and western blotting. The migration and invasion ability of ESCs was determined using wound healing and Transwell invasion assays, respectively. Compared with that from healthy individuals, miR-202 expression was demonstrated to be lower in the eutopic endometrium from patients with EMS, which was even lower in ectopic endometrium. Functional experiments in primary ESCs revealed that enhanced miR-202 expression suppressed the cell invasion and migration abilities, which was also accompanied with increased E-cadherin and reduced N-cadherin expression in ESCs, suggesting its potentially suppressive role in epithelial-mesenchymal transition. K-Ras is a well-known regulator of the ERK signaling pathway that was shown to be directly targeted and negatively regulated by miR-202. In addition, K-Ras expression was found to be upregulated in the ectopic endometrium, where it correlated negatively with that of miR-202. Knocking down K-Ras expression mimicked the anti-invasive effects of miR-202 overexpression on ESCs, whilst K-Ras overexpression attenuated the inhibitory role of miR-202 overexpression in ESC invasion. The K-Ras/Raf1/MEK/ERK signaling pathway was also blocked by miR-202 overexpression. These findings suggested that miR-202 inhibited ESC migration and invasion by inhibiting the K-Ras/Raf1/MEK/ERK signaling pathway, rendering miR-202 a candidate for being a therapeutic target for EMS.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway

et al. 2020

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“…Also, plasma membrane-associated ezrin enhances the migration and invasive potential of cancer cells ( 41 , 42 ). Finally, ezrin binding to membrane PIP 2 precedes phosphorylation at T567, thereby unmasking its membrane- and actin-binding sites necessary for ezrin conformational activation ( 43 ), potentially contributing to tumor progression ( 44 – 46 ).…”

Section: Discussionmentioning

confidence: 99%

Cotranslational interaction of human EBP50 and ezrin overcomes masked binding site during complex assembly

Khan

Long

Baleanu-Gogonea

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Multiprotein assemblages are the intracellular workhorses of many physiological processes. Assembly of constituents into complexes can be driven by stochastic, domain-dependent, posttranslational events in which mature, folded proteins specifically interact. However, inaccessibility of interacting surfaces in mature proteins (e.g., due to “buried” domains) can obstruct complex formation. Mechanisms by which multiprotein complex constituents overcome topological impediments remain enigmatic. For example, the heterodimeric complex formed by EBP50 and ezrin must address this issue as the EBP50-interacting domain in ezrin is obstructed by a self-interaction that occupies the EBP50 binding site. Here, we show that the EBP50-ezrin complex is formed by a cotranslational mechanism in which the C terminus of mature, fully formed EBP50 binds the emerging, ribosome-bound N-terminal FERM domain of ezrin during EZR mRNA translation. Consistent with this observation, a C-terminal EBP50 peptide mimetic reduces the cotranslational interaction and abrogates EBP50-ezrin complex formation. Phosphorylation of EBP50 at Ser339 and Ser340 abrogates the cotranslational interaction and inhibits complex formation. In summary, we show that the function of eukaryotic mRNA translation extends beyond “simple” generation of a linear peptide chain that folds into a tertiary structure, potentially for subsequent complex assembly; importantly, translation can facilitate interactions with sterically inaccessible domains to form functional multiprotein complexes.

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“…Besides these processes, various pathways such as the actin‐cytoskeleton pathway, Rap 1 signaling pathway, and phospholipase D signaling pathway were also identified. Once the actin‐cytoskeleton pathway is activated, it triggers the migration and invasion of the cells (C. Chen et al, 2020). Activation of the Rap 1 signaling pathway improves muscular dystrophy (Giannotta et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Expression profile and bioinformatics analysis of circular RNA in intestinal mucosal injury and repair after severe burns

Zhang

Hao

Deng

et al. 2020

Cell Biology International

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Circular RNA (circRNA) is a novel noncoding RNA that is mostly found in humans and animals. Although the flux of circRNA research has increased in recent years, its precise function is still unclear. Some studies demonstrate that circRNAs can function as microRNA (miRNA) sponges involved in the regulation of competitive endogenous RNAs networks and play a crucial role in many biological processes. Other studies show that circRNAs play multiple biological roles in gastrointestinal diseases. However, the expression characteristics and function of circRNA in intestinal mucosal injury and repair after severe burn have not been reported. This study aims to screen differentially expressed circRNAs in intestinal mucosal injury and repair after severe burns and understand their underlying mechanisms. To test our hypothesis that circRNA may play a role in promoting repair in intestinal mucosa injury after severe burns, we collected the intestinal tissues of three severely burned mice and three pseudo‐scalded mice and evaluated the expression of circRNAs via microarray analysis. Quantitative real‐time polymerase chain reaction was also used to validate the circRNA microarray data by selecting six based on different multiples, original values, and p values. The host genes of all differentially expressed circRNAs and the downstream target genes of six selected DEcircRNAs were identified by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Meanwhile, we also created a circRNA‐miRNA‐mRNA network to predict the role and function of circRNAs in intestinal mucosal injury and repair after severe burns.

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Ezrin T567 phosphorylation regulates migration and invasion of ectopic endometrial stromal cells by changing actin cytoskeleton

Cited by 16 publications

References 24 publications

MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway

MicroRNA‑202 inhibits endometrial stromal cell migration and invasion by suppressing the K‑Ras/Raf1/MEK/ERK signaling pathway

Cotranslational interaction of human EBP50 and ezrin overcomes masked binding site during complex assembly

Expression profile and bioinformatics analysis of circular RNA in intestinal mucosal injury and repair after severe burns

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