microRNAs expression in endometriosis and their relation to angiogenic factors

Ramón, Luis A.; Braza-Boïls, Aitana; Gilabert-Estellés, Juan; Gilabert, J.; España, Francisco; Chirivella, Melitina; Estellés, Amparo

doi:10.1093/humrep/der025

Cited by 103 publications

(51 citation statements)

References 41 publications

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“…For example, the miR-200 family has been reported to be highly expressed in EEC compared with normal endometrial tissues and may play an important role in cancer growth (17). In uterine disorders, miR-21 has been found to be associated with endometriosis, leiomyoma and cervical cancer (18,19). However, the exact role of miR-21 in EEC is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer

et al. 2012

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Abstract. The aim of this study was to investigate the role of microRNA-21 (miR-21) in the regulation of phosphatase and tensin homolog deleted from chromosome-10 (PTEN) expression and proliferation of endometrioid endometrial cancer (EEC) cells. We performed a qRT-PCR assay with miR-21 and PTEN in 16 paired EEC tumor tissues and adjacent non-tumor endometrium. To investigate the regulation of PTEN by miR-21, we designed gain-and loss-of-function of miR-21 experiments in the KLE cell line by transfection with a synthetic miR-21 mimic and inhibitor. To validate the putative binding site of miR-21 in the 3' untranslated region (3'-UTR) of PTEN messenger RNA (mRNA), a dual-luciferase reporter assay was carried out. To evaluate the potential effect of miR-21 on EEC proliferation, we performed both overexpression experiments, using an miR-21 mimic, and inhibition assays, using an miR-21 inhibitor. miR-21 was overexpressed in EEC and was inversely correlated with PTEN protein expression (P<0.001). miR-21 regulated PTEN protein expression and cell proliferation in the KLE cell line and the direct binding of miR-21 to the PTEN 3'-UTR was confirmed using a dual-luciferase reporter assay. The upregulation of miR-21 led to a significant decrease in the PTEN protein expression level (P=0.007). The downregulation of miR-21 led to a significant increase in PTEN protein (P=0.002). The expression of luciferase in the wt-PTEN-3'-UTR-pGL3 group was downregulated in the presence of the miR-21 mimic (P=0.001). miR-21 was overexpressed in EEC. In conclusion, we demonstrated that the expression of PTEN protein, but not mRNA, was negatively directly regulated by miR-21 in the KLE cell line. The overexpression of miR-21 modulated EEC cell proliferation through the downregulation of PTEN.

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Section: Discussionmentioning

confidence: 99%

microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer

et al. 2012

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“…[7][8][9] In human endometrium, several studies, including next generation sequencing have identified the expression of a large number of miRNAs, some of which showed altered expression in endometriosis and endometrial cancer. [10][11][12][13][14][15][16][17] Among those altered in endometriosis and endometrial cancer, include the members of miR-200 family: miR-200c/141 and miR-200b/200a/429 clusters. 11,13,15,[18][19][20][21][22] The expression and function of miR-200 family has been well documented in various tissues and cells, where they target the expression of many genes, including ZEBs, the transcription factors that regulate cellular transformation, more specifically epithelial-to-mesenchymal transition (EMT) during cancer development and progression through repression of adhesion molecules such as E-cadherin.…”

Section: Introductionmentioning

confidence: 99%

Endometrial miR-200c is Altered During Transformation into Cancerous States and Targets the Expression of ZEBs, VEGFA, FLT1, IKKβ, KLF9, and FBLN5

et al. 2012

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A number of microRNAs (miRNAs), including miR-200 family, are aberrantly expressed in endometriosis and endometrial cancer. Here we assessed the expression and functional aspects of miR-200c in endometrial tissues (N ¼ 52) from normal endometrial biopsies (N ¼ 15), endometrial tissues including those exposed to hormonal therapies (N ¼ 20), and grade I-III endometrial cancer (N ¼ 17). miR-200c expression was elevated in normal endometrial biopsies from mid-and late-luteal phase, and in endometrial tumors as compared to endometrial tissues from peri-and postmenopausal period (P < .05) and its pattern of temporal expression displayed an inverse relationship with the expression of ZEBs. The expression of E-cadherin (CDH1) varied, but expressed at low levels, specifically in endometrial tissues and endometrial tumors. The endometrial expression of ZEBs and CDH1 in patients who were exposed to Depo-Provera and gonadotropin-releasing hormone agonist GnRHa displayed a trend toward lower expression as compared to proliferative phase; however, treatment of Ishikawa cells with 17b-estradiol, progesterone, and medroxy progesterone acetate had modest effects on the expression of miR-200c and ZEBs without affecting CDH1 expression. Gain of function of miR-200c in Ishikawa cells repressed ZEBs, as well as VEGFA, FLT1, IKKb, and KLF9 expression at transcriptional and translational levels through direct interaction with their respective 3 0 untranslated regions and increased the rate of their proliferation. These results indicated that endometrial miR200c expression undergoes dynamic changes during transition from normal into cancerous states; possibly influenced by hormonal milieu and by targeting the expression of specific genes with key regulatory functions in cellular transformation, inflammation, and angiogenesis may influence these events during normal and disease progression.

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“…Takehara et al 32 have reported an increase in VEGF mRNA expression in endometriotic tissue (early stages) compared with the eutopic endometrium. However, in some previous reports, the authors found that ovarian endometriomas had lower VEGF levels and higher TSP-1 levels compared to eutopic endometrium or peritoneal lesions [9][10][11] and thought that 3 clinically distinct lesions of endometriosis, including peritoneal lesion, ovarian endometrioma, and deep infiltrating endometriosis, may be variants of the same pathologic process, or they may be caused by different mechanisms. 22,33 In the present study, we did not detect any increase in VEGF levels or any decrease in TSP-1 in ovarian endometrioma and even found a lower VEGF level and a higher TSP-1 level in comparison with ovarian tissues surrounding the mature teratoma that is a benign tumor without the capabilities of invasiveness and metastasis.…”

Section: Discussionmentioning

confidence: 93%

“…However, in some published reports, the authors found that ovarian endometriomas had lower levels of VEGF and higher levels of TSP-1 compared to eutopic endometrium or peritoneal lesions. [9][10][11] If so, how does this condition initiate and develop with low capabilities of angiogenesis and metastasis?…”

Section: Introductionmentioning

confidence: 99%

Influence of Ovarian Endometrioma on Expression of Steroid Receptor RNA Activator, Estrogen Receptors, Vascular Endothelial Growth Factor, and Thrombospondin 1 in the Surrounding Ovarian Tissues

Lin

et al. 2014

Reprod. Sci.

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This study investigates the influence of ovarian endometrioma on expression of steroid receptor RNA activator (SRA), estrogen receptors (ERs), vascular endothelial growth factor (VEGF), and thrombospondin 1 (TSP-1) in the surrounding ovarian tissues. Taken from the women with ovarian endometrioma and mature teratoma during laparoscopy, the biopsies were analyzed by realtime polymerase chain reaction and Western blot. Our results indicated that ovarian tissues surrounding endometrioma had lower SRA and ER-a levels but higher SRA protein (SRAP) and ER-b levels than ovarian endometrioma. With lower VEGF levels and higher TSP-1 levels, the surrounding ovarian tissues showed higher expression levels of SRA, SRAP, ER-a, and ER-b in the ovarian endometrioma group when compared to the controls. These data showed that ovarian endometrioma increases SRA, ERs, and TSP-1 but decreases VEGF levels in the surrounding ovarian tissues, suggesting that abnormal expression of these molecules may affect biological behaviors of ovarian endometrioma.

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microRNAs expression in endometriosis and their relation to angiogenic factors

Abstract: Expression levels of miRNAs related to angiogenesis were different in eutopic endometrium from that observed in ovarian endometrioma. This could influence the expression of angiogenic factors and play a role in the pathogenesis of endometriosis.

Cited by 103 publications

References 41 publications

microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer

microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer

Endometrial miR-200c is Altered During Transformation into Cancerous States and Targets the Expression of ZEBs, VEGFA, FLT1, IKKβ, KLF9, and FBLN5

Influence of Ovarian Endometrioma on Expression of Steroid Receptor RNA Activator, Estrogen Receptors, Vascular Endothelial Growth Factor, and Thrombospondin 1 in the Surrounding Ovarian Tissues

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