miR-45la Inhibition Reduces Established Endometriosis Lesions in Mice
- PDF / 345,013 Bytes
- 6 Pages / 602.986 x 782.986 pts Page_size
- 74 Downloads / 181 Views
miR-451a Inhibition Reduces Established Endometriosis Lesions in Mice
Reproductive Sciences 1-6 ยช The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1933719119862050 journals.sagepub.com/home/rsx
Menghui Li, MD, PhD1, Yuping Zhou, BS1, and Hugh S. Taylor, MD1
Abstract Endometriosis is an estrogen-dependent pro-inflammatory disease that affects 6% to 10% of reproductive-age women. Current treatments target sex steroids, and none are disease-specific. MicroRNA treatments have provided promising results for some chronic diseases and cancers. We have previously shown microRNA 451a is increased in endometriosis and that elevation of 451a contributes to the pathophysiology of the disease. Here, we propose inhibition of miR-451a for the treatment of endometriosis in a murine model. Endometriosis was treated using a microRNA 451a inhibitor or a scrambled control microRNA. Treatment with miR-451a inhibitor resulted in reduced endometriosis lesion size (30 vs 13 mm3). There was no difference in the number of visible lesions between the miR-451a treatment and controls. Treatment led to altered expression of several genes including YWHAZ, CAB39, MAPK1, b-catenin, and IL-6. Systemic treatment with a miR-451a inhibitor is a promising therapy for endometriosis that simultaneously affects multiple pathways driving the disease. Keywords endometriosis, microRNA, miR-451, oligonucleotide treatment
Background Endometriosis is an estrogen-dependent pro-inflammatory disease; 6% to 10% of reproductive-age women have infertility and pelvic pain resulting from endometriosis.1-4 Due to the chronic morbidity associated with this gynecological disorder, past studies have attempted to identify distinguishing molecular features of the endometriotic lesions with the aim of developing more effective prognostic, diagnostic, and/or treatment strategies for the clinical management.1,2 Despite such efforts, however, many current clinical treatments are inadequate for symptom relief and have unacceptable side effects.5 All current treatments target sex steroids, and none are disease-specific. A precision medicine approach to endometriosis may allow treatment for endometriosis without the adverse effects of hormone modification such as impaired fertility, vasomotor symptoms, or bone loss. MicroRNAs (miRNAs) are endogenous, short, noncoding, functional RNAs that regulate gene expression either by translational repression or by degradation of messenger RNA (mRNA) transcripts.6 Numerous noncoding RNAs including miRNAs are expressed in endometrium and endometriosis.7,8 Differential expression of multiple miRNAs has been identified between eutopic endometrium of women with and without endometriosis, in the circulation of women with and without endometriosis, and in murine experimental endometriosis, and between eutopic and ectopic endometrial tissues from women with endometriosis.9-16
Of those miRNAs dysregulated in endometriotic tissue, miR-451a is of specific interest. MiR-451a functions in a variety of physiol
Data Loading...
