Aromatase inhibitor regulates let-7 expression and let-7f–induced cell migration in endometrial cells from women with endometriosis

Cho, SiHyun; Mutlu, Levent; Zhou, Yamei; Taylor, Hugh S.

doi:10.1016/j.fertnstert.2016.05.020

Cited by 63 publications

(56 citation statements)

References 22 publications

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“…They also identified a Let‐7f binding site in Cyp19a1, indicating that the aromatase gene is a direct target of Let‐7f . We demonstrated similar results in endometrial stromal cells from endometriosis patients and in Ishikawa cells . In our study, significantly increased Let‐7b and Let‐7f expression levels were determined after aromatase inhibitor treatment.…”

Section: Discussionsupporting

confidence: 85%

“…Accordingly, 1.0 mL 5% glucose mixture including 100 μg nucleic acid and 16 μL carrier reagent (N/P = 8) was prepared for each injection, and mice were treated by intraperitoneal injections for every 3 days for 2 weeks. The dose chosen was based on our previously described in vitro dose–response experiments …”

Section: Methodsmentioning

confidence: 99%

“…13 We previously reported that circulating microRNAs, including Let-7b-5p, were significantly decreased in the serum of patients with endometriosis as well as animal models of the 14,15 Further, we have reported decreased Let-7 family members in endometriosis tissue where they are involved in the regulation of genes such as KRAS and aromatase. 16,17 These studies prompted us to hypothesize that miRNA Let-7b-5p might have a major role in the pathogenesis and treatment of endometriosis.…”

Section: Introductionmentioning

confidence: 99%

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microRNA Let‐7b: A Novel treatment for endometriosis

Şahin

Mamillapalli

et al. 2018

J Cellular Molecular Medi

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Endometriosis is an oestrogen‐dependent, chronic inflammatory disease that affects 10% of reproductive‐aged women. Current treatment options depend on female sex steroid hormone modulation; however, all have side effects and are not useful in women who want to conceive. microRNAs treatments have provided promising results for some chronic diseases and cancers. We have previously shown the microRNA Let‐7b is repressed in endometriosis and that loss of Let‐7 contributes to the pathophysiology of the disease. Here, we propose using microRNA Let‐7b for the treatment of endometriosis in a murine model. Endometriosis was treated using microRNA Let‐7b or a scrambled control microRNA. Let‐7b treatment resulted in reduced endometriosis lesion size. Decreased gene expression was noted in several genes known to promote endometriosis growth including ER‐α, ER‐ß, Cyp19a, KRAS 4A, KRAS 4B and IL‐6. These results indicate that microRNA Let‐7b has a pleiotropic role in endometriosis pathophysiology affecting oestrogen signalling, inflammation and growth factor receptors. Local treatment of endometriosis with Let‐7b is a promising therapy for endometriosis that simultaneously affects multiple pathways driving endometriosis without systemic hormonal side effects.

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Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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microRNA Let‐7b: A Novel treatment for endometriosis

Şahin

Mamillapalli

et al. 2018

J Cellular Molecular Medi

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“…The paucity of AU‐rich regions in the target sequence would argue against the involvement of traditional RNA‐binding proteins involved in RNA stability as they are expressed in many cell types (Bevilacqua, Ceriani, Capaccioli, & Nicolin, ). MicroRNAs also interact with 3′UTRs, and miR‐let‐7f inhibited CYP19A1 mRNA levels in human endometrial cells (Cho, Mutlu, Zhou, & Taylor, ) and binds to the 3′‐UTR of human CYP19A1 in breast cancer cell‐lines (Shibahara et al, ). Other miRNAs that have been shown to bind to the porcine CYP19A1 3′UTR are miR‐378 and miR‐10b (Li, Du, Pan, Zhang, & Li, ; Xu, Linher‐Melville, Yang, Wu, & Li, ), but recognition sites for none of these miRNAs were predicted in the bovine region of interest.…”

Section: Discussionmentioning

confidence: 99%

A putative protein–RNA complex regulates posttranscriptional processing of cytochrome P450 aromatase (CYP19A1) in bovine granulosa cells

Sahmi

Gévry

et al. 2019

Molecular Reproduction Devel

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Follicle growth and granulosa cell health are dependent on the secretion of estradiol from granulosa cells. Estradiol is synthesized from androgen precursor by cytochrome P450 aromatase (CYP19A1), and in cattle CYP19A1 messenger RNA has a short half‐life but a long (3.5 kb) 3′‐untranslated region (3′UTR), suggesting that posttranscriptional regulation may be important for control of enzyme activity. We tested this hypothesis by inserting the CYP19A1 3′UTR and fragments thereof into a reporter vector between the end of the luciferase coding region and the polyadenylation signal. The full‐length aromatase 3′UTR suppressed luciferase activity to 10% of control levels, and smaller fragments showed that this inhibitory activity lies between +926 and +1134 of the 3′UTR. Protein–RNA cross‐linking experiments revealed that these 3′UTR fragments formed an RNA–protein complex of approximately 70 kDa that was present in granulosa cells but not in corpus luteum, lung, liver, kidney, pancreas, or bladder extracts. The RNA‐binding activity was specific to the 3′UTR, as shown by competition experiments with unlabeled RNA, and was present only in 3′UTR constructs that inhibited luciferase activity. These data suggest that posttranscriptional regulation is an important component of the control of CYP19A1 expression and involves protein binding to a specific sequence in the 3′UTR.

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“…5 Moreover, let-7f exhibits an in vitro therapeutic effect on endometriotic stromal cells. These data collectively led us to speculate locally produced estrogen may suppress beneficial microRNA species and thus aggravate the pathologic features of endometriosis, whereas aromatase inhibitors via an intracrine effect stimulate the expression of members of the let-7f family to suppress and treat endometriosis (Figure 1).…”

mentioning

confidence: 99%