miR-196b targets c-myc and Bcl-2 expression, inhibits proliferation and induces apoptosis in endometriotic stromal cells

Abe, Wakana; Nasu, Kaei; Nakada, Chisato; Kawano, Yukie; Moriyama, Masatsugu; Narahara, Hisashi

doi:10.1093/humrep/des446

Cited by 99 publications

(100 citation statements)

References 40 publications

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“…However, Saare et al (2014) found that miR-200b was upregulated in such tissues. In addition, miR-20a plays an important role in the pathogenesis of ovarian endometriosis by suppressing NTN4 (Zhao et al, 2014), miR23a and miR23b are potential biomarkers of ovarian endometriosis (Shen et al, 2013), and miR196b targets c-myc and Bcl-2 expression, inhibiting proliferation and inducing apoptosis in endometriotic stromal cells (Abe et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

Teng

et al. 2016

Genet. Mol. Res.

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ABSTRACT. We examined the aberrant microRNA (miRNA) expression profile responsible for the changes in angiogenesis observed in endometriotic lesions. This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient, and their correlation with the most important angiogenic and fibrinolytic factors. miRNA expression was quantified using a microRNA array and reversetranscription microRNA polymerase chain reaction. Levels of vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor 2 (EGFR2), phosphatase and tensin homolog (PTEN), and C-X-C chemokine receptor type 4 (CXCR4) were quantified using enzyme-linked immunosorbent assay. The endometrial tissue showed significantly lower levels of miR-200b, miR-15a-5p, miR-19b-1-5p, miR-146a-5p, and miR-200c, and higher levels of miR-16-5p, miR106b-5p, and miR-145-5p. VEGFA was significantly upregulated, whereas EGFR2, PTEN, and CXCR4 were markedly downregulated, in the endometriotic tissues compared to that in the normal endometrial tissues. In conclusion, differences in the miRNA levels could modulate the expression of VEGFA, EGFR2, PTEN, and CXCR4, and may play an important role in the pathogenesis of endometriosis. The higher angiogenic and proteolytic activities observed in the eutopic endometrium might facilitate the implantation of endometrial cells at ectopic sites.

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Section: Discussionmentioning

confidence: 99%

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

Teng

et al. 2016

Genet. Mol. Res.

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“…The occurrence and development of endometriosis may be based on these aberrations in molecular processes, and may be caused by as yet unknown triggers, including miRNA, which initiate these molecular alterations. Certain studies have investigated the role of miRNA expression dysregulation, histone modification and DNA methylation in endometriotic cells (17). Aberrant gene expression associated with epigenetic mechanisms may induce differentiation and the subsequent appearance of an endometriotic phenotype in healthy endometrial cells (15,16).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiles and networks in CXCL12-stimulated human endometrial stromal cells

Mei

et al. 2016

Molecular Medicine Reports

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The chemokine stromal cell-derived factor-1 (C-X-C motif chemokine ligand 12; CXCL12) is important in the recruitment of leukocytes to the peritoneal cavity and the regulation of endometriotic tissue growth in endometriosis patients. However, the alterations in microRNA (miRNA) expression induced by CXCL12 remain to be fully elucidated. The present study evaluated key miRNAs in CXCL12-stimulated endometrial stromal cells (ESCs), and investigated the underlying cellular regulatory mechanisms of CXCL12 in endometriosis by building networks between miRNAs, genes and gene ontologies (GOs). Differential expression of miRNAs and mRNAs induced by CXCL12 stimulation in ESCs was measured using miRNA and gene chips, and it was observed that 35 miRNAs and 1,671 mRNAs were differentially expressed. Using potential target genes of the 35 miRNAs, intersections of these genes were examined and 63 intersection genes were identified. A total of 39 GOs were obtained for these intersection genes, based on information from GO databases, including immune cell chemoattractants, inflammatory and immune responses, and pathological processes of endometriotic lesions in endometriosis. In addition, miRNA-gene networks were built according to the GO and Kyoto Encyclopedia of Genes and Genomes databases. The present study, to the best of our knowledge, provides the most complete miRNAome and mRNAome profiles, and the most detailed investigation of the underlying cellular regulatory mechanisms, of the effects of CXCL12 in endometriosis. These results may facilitate the complete elucidation of the role of CXCL12 in endometriosis, and its underlying epigenetic mechanisms.

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“…Most recently, Abe and colleagues (2013) examined the miRNA profiles in endometriotic versus eutopic endometrial stromal cells. Stromal cells were isolated from ovarian endometriomas, while endometrial stromal cells were obtained from eutopic endometrium of women with leiomyomas but no visible signs of endometriosis.…”

Section: 3 Mirnas In Endometrial Physiology and Pathologymentioning

confidence: 99%

“…Right table summarizes miRNAs and their predicted transcript/protein in endometriotic tissue (indicated as red ectopic tissue in the figure) derived from studies incorporating human cells which have been validated. Superscripts refer to references with a = Petracco et al 2011; b = Hawkins et al 2011; c = Abe et al 2013; d = Dai et al 2012; e = Shen et al 2013; f = Adammek et al 2013. Validation refers to either assessing cellular events and/or mRNA and protein levels by modulation of endogenous miRNA levels…”

Section: Fig 91mentioning

confidence: 99%

Non-coding RNAs in Uterine Development, Function and Disease

Nothnick

2015

Advances in Experimental Medicine and Biology

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The major function of the uterus is to accept and provide a suitable environment for an embryo, ultimately leading the birth of offspring and successful propagation of the species. For this occur, there must be precise coordination of hormonal signalling within both the endometrial and myometrial components of this organ. Non-coding RNAs, specifically, microRNAs (miRNAs) have been shown to be essential for normal uterine development and function. Within this organ, miRNAs are proposed to fine-tune the actions of the female steroid hormones estradiol and progesterone. Not surprising, mis-expression of miRNAs has been documented in diseases of the endometrium and myometrium such as endometriosis and leiomyomas, respectively. In this chapter, I will review the current understanding on the role, regulation and function of non-coding RNAs focusing on miRNAs in both the normal physiology of the endometrium and myometrium as well as in pathologies of these tissues, namely endometriosis and leiomyomas.

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miR-196b targets c-myc and Bcl-2 expression, inhibits proliferation and induces apoptosis in endometriotic stromal cells

Abstract: This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 20591920 to K.N. and no. 23592407 to H.N.) and The Uehara Memorial Foundation (to K.N.).

Cited by 99 publications

References 40 publications

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

MicroRNA expression profiles and networks in CXCL12-stimulated human endometrial stromal cells

Non-coding RNAs in Uterine Development, Function and Disease

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