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miR-196b targets c-myc and Bcl-2 expression, inhibits proliferation and induces apoptosis in endometriotic stromal cells.
Hum Reprod. 2013 Mar; 28(3):750-61.HR

Abstract

STUDY QUESTION

What is the global expression pattern of microRNAs (miRNAs) in endometriotic stromal cells and is miR-196b involved in the pathogenesis of endometriosis?

SUMMARY ANSWER

Several miRNAs are aberrantly expressed in endometriotic cyst stromal cells (ECSCs), including miR-196b whose expression is repressed in endometriotic stromal cells.

WHAT IS KNOWN ALREADY

Although, histologically, endometriotic tissues and normal proliferative endometrium are similar, a number of distinct molecular differences have been reported to date. The anti-apoptotic and excessive proliferative properties of endometriotic cells are considered to be involved in the development and progression of endometriosis.

STUDY DESIGN AND SIZE DURATION

ECSCs and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues and eutopic endometrial tissues, respectively and compared.

PARTICIPANTS/MATERIALS, SETTING AND METHODS

Aberrantly expressed miRNAs in ECSCs were identified by a global miRNA microarray technique. The roles of miR-196b in ECSC proliferation, apoptosis, and c-myc and B-cell lymphoma/leukemia (Bcl)-2 mRNA expression were investigated with precursor hsa-miR-196b transfection. The methylation status of the miR-196b gene in ECSCs and the effect of a DNA demethylating agent on miR-196b expression were also examined.

MAIN RESULTS AND THE ROLE OF CHANCE

miRNA microarray analysis identified eight down-regulated miRNAs (including miR-196b) and four up-regulated miRNAs in ECSCs. Compulsory expression of miR-196b directed the inhibition of proliferation and the induction of apoptosis in ECSCs. miR-196b was found to suppress c-myc and Bcl-2 mRNA expression in ECSCs, and there was a significant correlation between miR-196b and HOXA10 expression in ECSCs and NESCs. The miR-196b gene was hypermethylated in ECSCs when compared with NESCs, and the treatment with a DNA demethylating agent restored the expression of miR-196b in ECSCs.

LIMITATIONS AND REASONS FOR CAUTION

miRNA expression profiles were investigated only in the stromal component of ectopic and eutopic endometrium samples. In addition to miR-196b, the roles of other miRNAs aberrantly expressed in ECSCs should be examined.

WIDER IMPLICATIONS OF THE FINDINGS

The present findings suggest that aberrant miRNA expression plays an important role in the pathogenesis of endometriosis as a part of epigenetic mechanisms, that expression of miR-196b in ECSCs is repressed by DNA hypermethylation of the miR-196b gene and this repression may be involved in the development of proliferative and anti-apoptotic characteristics of endometriosis.

STUDY FUNDING

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.).

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23293219

Citation

Abe, Wakana, et al. "MiR-196b Targets C-myc and Bcl-2 Expression, Inhibits Proliferation and Induces Apoptosis in Endometriotic Stromal Cells." Human Reproduction (Oxford, England), vol. 28, no. 3, 2013, pp. 750-61.
Abe W, Nasu K, Nakada C, et al. MiR-196b targets c-myc and Bcl-2 expression, inhibits proliferation and induces apoptosis in endometriotic stromal cells. Hum Reprod. 2013;28(3):750-61.
Abe, W., Nasu, K., Nakada, C., Kawano, Y., Moriyama, M., & Narahara, H. (2013). MiR-196b targets c-myc and Bcl-2 expression, inhibits proliferation and induces apoptosis in endometriotic stromal cells. Human Reproduction (Oxford, England), 28(3), 750-61. https://doi.org/10.1093/humrep/des446
Abe W, et al. MiR-196b Targets C-myc and Bcl-2 Expression, Inhibits Proliferation and Induces Apoptosis in Endometriotic Stromal Cells. Hum Reprod. 2013;28(3):750-61. PubMed PMID: 23293219.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - miR-196b targets c-myc and Bcl-2 expression, inhibits proliferation and induces apoptosis in endometriotic stromal cells. AU - Abe,Wakana, AU - Nasu,Kaei, AU - Nakada,Chisato, AU - Kawano,Yukie, AU - Moriyama,Masatsugu, AU - Narahara,Hisashi, Y1 - 2013/01/04/ PY - 2013/1/8/entrez PY - 2013/1/8/pubmed PY - 2013/8/24/medline SP - 750 EP - 61 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 28 IS - 3 N2 - STUDY QUESTION: What is the global expression pattern of microRNAs (miRNAs) in endometriotic stromal cells and is miR-196b involved in the pathogenesis of endometriosis? SUMMARY ANSWER: Several miRNAs are aberrantly expressed in endometriotic cyst stromal cells (ECSCs), including miR-196b whose expression is repressed in endometriotic stromal cells. WHAT IS KNOWN ALREADY: Although, histologically, endometriotic tissues and normal proliferative endometrium are similar, a number of distinct molecular differences have been reported to date. The anti-apoptotic and excessive proliferative properties of endometriotic cells are considered to be involved in the development and progression of endometriosis. STUDY DESIGN AND SIZE DURATION: ECSCs and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues and eutopic endometrial tissues, respectively and compared. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Aberrantly expressed miRNAs in ECSCs were identified by a global miRNA microarray technique. The roles of miR-196b in ECSC proliferation, apoptosis, and c-myc and B-cell lymphoma/leukemia (Bcl)-2 mRNA expression were investigated with precursor hsa-miR-196b transfection. The methylation status of the miR-196b gene in ECSCs and the effect of a DNA demethylating agent on miR-196b expression were also examined. MAIN RESULTS AND THE ROLE OF CHANCE: miRNA microarray analysis identified eight down-regulated miRNAs (including miR-196b) and four up-regulated miRNAs in ECSCs. Compulsory expression of miR-196b directed the inhibition of proliferation and the induction of apoptosis in ECSCs. miR-196b was found to suppress c-myc and Bcl-2 mRNA expression in ECSCs, and there was a significant correlation between miR-196b and HOXA10 expression in ECSCs and NESCs. The miR-196b gene was hypermethylated in ECSCs when compared with NESCs, and the treatment with a DNA demethylating agent restored the expression of miR-196b in ECSCs. LIMITATIONS AND REASONS FOR CAUTION: miRNA expression profiles were investigated only in the stromal component of ectopic and eutopic endometrium samples. In addition to miR-196b, the roles of other miRNAs aberrantly expressed in ECSCs should be examined. WIDER IMPLICATIONS OF THE FINDINGS: The present findings suggest that aberrant miRNA expression plays an important role in the pathogenesis of endometriosis as a part of epigenetic mechanisms, that expression of miR-196b in ECSCs is repressed by DNA hypermethylation of the miR-196b gene and this repression may be involved in the development of proliferative and anti-apoptotic characteristics of endometriosis. STUDY FUNDING: 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.). SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/23293219/miR_196b_targets_c_myc_and_Bcl_2_expression_inhibits_proliferation_and_induces_apoptosis_in_endometriotic_stromal_cells_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/des446 DB - PRIME DP - Unbound Medicine ER -