Dysfunctional signaling underlying endometriosis: current state of knowledge

Cho, Yeon Jean; Lee, Seung Hyun; Park, Jung‐Woo; Han, Myoungseok; Park, Mi Jin; Han, Sang Jun

doi:10.1530/jme-17-0227

Cited by 33 publications

(26 citation statements)

References 144 publications

(148 reference statements)

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“…MALAT1 increase expression of NF-κB which in turn binds with PGE-2 to enhance its expression ( 99 ). PGE-2 activates BCL2/BAX through interaction with EP2/EP4 receptor and suppresses intrinsic apoptotic pathway ( 100 ). PGE2 also activates cell proliferation through EP2/EP3 ( 101 ).…”

Section: Lncrnas and Endometriosismentioning

confidence: 99%

Role of Non-coding RNAs in the Pathogenesis of Endometriosis

2020

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Endometriosis is a disorder characterized by the presence of endometrial glands and stroma like lesions outside of the uterus. Although several hypothesis have tried to explain the underlying cause of endometriosis, yet the main cause remained obscure. Recent studies have shown contribution of non-coding RNAs in the pathogenesis of endometriosis. Two classes of these transcripts namely long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have mostly attracted attention of researchers. Several studies have reported aberrant expression of these transcripts in affected tissues from patients as well as animal models. Modulation of important signaling pathways such as PI3K/AKT, P38-MAPK, ERK1/2-MAPK and Wnt-β catenin by miRNAs and lncRNAs have potentiated these molecules as biomarkers or therapeutic agents in endometriosis. Single nucleotide polymorphisms with miR-126, miR-143 and miR-146b have been associated with risk of endometriosis. Moreover, miRNAs and lncRNAs control inflammatory responses, cell proliferation, angiogenesis and tissue remodeling, thus understanding the role of these transcripts in endometriosis is a possible way to develop novel diagnostic tests and therapeutic targets for this disorder.

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Section: Lncrnas and Endometriosismentioning

confidence: 99%

Role of Non-coding RNAs in the Pathogenesis of Endometriosis

2020

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“…These alterations are summarized in Table 4. Although endometriosis is considered a ‘benign’ disease, it resembles the biologic behavior of malignant cells [113,114], and a change in the expression of various junctional proteins may support the invasive properties of this tissue and may facilitate its growth at ectopic localizations. Moreover, these impairments may also contribute to endometriosis-associated infertility.…”

Section: Direct Cell–cell Interactions In Endometrial Pathophysiologymentioning

confidence: 99%

Direct Cell–Cell Interactions in the Endometrium and in Endometrial Pathophysiology

Grund

Grümmer

2018

IJMS

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Cell contacts exhibit a considerable influence on tissue physiology and homeostasis by controlling paracellular and intercellular transport processes, as well as by affecting signaling pathways. Since they maintain cell polarity, they play an important role in cell plasticity. The knowledge about the junctional protein families and their interactions has increased considerably during recent years. In contrast to most other tissues, the endometrium undergoes extensive physiological changes and reveals an extraordinary plasticity due to its crucial role in the establishment and maintenance of pregnancy. These complex changes are accompanied by changes in direct cell–cell contacts to meet the various requirements in the respective developmental stage. Impairment of this sophisticated differentiation process may lead to failure of implantation and embryo development and may be involved in the pathogenesis of endometrial diseases. In this article, we focus on the knowledge about the distribution and regulation of the different junctional proteins in the endometrium during cycling and pregnancy, as well as in pathologic conditions such as endometriosis and cancer. Decoding these sophisticated interactions should improve our understanding of endometrial physiology as well as of the mechanisms involved in pathological conditions.

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“…Recent studies have found that repeated cyclical haemorrhage is involved in the initiation and progression of endometriosis via inducing excessive oxidative stress (OS) 2 , which is defined as an imbalance between reactive oxygen species (ROS) and antioxidants 3,4 . Many studies on OS-associated diseases suggest that oxidative balance is complicated and precarious 5 , as ROS not only modifies proteins, impacts lipids, damages DNA strand structure and regulates cell cycle checkpoints 6,7 , but also maintains survival, intensifies adhesion, promotes angiogenesis and facilitates cell cycle progression 8–10 . In endometriosis, excessive OS results in higher DNA damage and reduced DNA repair activity 3,11 .…”

Section: Introductionmentioning

confidence: 99%

MiR-210-3p protects endometriotic cells from oxidative stress-induced cell cycle arrest by targeting BARD1

Dai

Lin

et al. 2019

Cell Death Dis

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Endometriosis is associated with benign but adversely developed cysts in the extrauterine environment. The oxidative imbalanced environment induces DNA damage and affects cell cycle progression of endometrial stromal cells (ESCs) and endometrial epithelial cells, but how endometriotic cells maintain proliferation in the presence of oxidative stress is not clear. Growing evidence has indicated that the ectopic hypoxic microenvironment and oxidative stress can stimulate the growth of endometriotic cells, which is mainly due to the increase of HIF-1α. We found that the master hypoxia-associated miRNA miR-210-3p was increased in stromal and glandular cells of ectopic lesions compared with that of eutopic and normal endometria and was consistent with the expression of HIF-1α and the local oxidative stress-induced DNA damage predictor 8-OHdG. Moreover, miR-210-3p was upregulated in ESCs and Ishikawa cells under hypoxic conditions but not in normoxic culture. Knockdown of miR-210-3p induced a G2/M arrest of ESCs and Ishikawa cells under hypoxia, while no effect was found under normoxia. BARD1 was identified as a target of miR-210-3p. BARD1 expression was decreased in endometriotic tissues compared with eutopic and normal endometria and negatively correlated with the expression of miR-210-3p. Multivariate regression analysis showed that BARD1 downregulation could serve as an indicator for endometriotic severity. Our results suggest that miR-210-3p attenuates the G2/M cell cycle checkpoint by inactivating BRCA1 complex function in response to DNA damage under hypoxia via targeting the 3′ untranslated region of BARD1 mRNA. Endometriotic mouse model experiments showed that intraperitoneal injection of the miR-210-3p inhibitor or vitamin C suppressed the growth of endometriotic lesions. Together, our results demonstrate that endometriotic cells inhibit BARD1/BRCA1 function by upregulating miR-210-3p, which might be the underlying mechanism for endometriotic cell maintenance of growth in oxidative stress. Furthermore, inhibition of miR-210-3p and administration of vitamin C are promising approaches for the treatment of endometriosis.

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Dysfunctional signaling underlying endometriosis: current state of knowledge

Abstract: 14Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. It

Cited by 33 publications

References 144 publications

Role of Non-coding RNAs in the Pathogenesis of Endometriosis

Role of Non-coding RNAs in the Pathogenesis of Endometriosis

Direct Cell–Cell Interactions in the Endometrium and in Endometrial Pathophysiology

MiR-210-3p protects endometriotic cells from oxidative stress-induced cell cycle arrest by targeting BARD1

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