Down-Regulation of miR-93 Negatively Correlates with Overexpression of VEGFA and MMP3 in Endometriosis: A Cross-Sectional Study

Document Type : Original Article


1 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

2 Human Reproduction, Infertility, and Family Planning Research Center, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

3 Yasmin IVF Clinic, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia

4 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia


Background: Endometriosis is identified as presence of the endometrium outside the uterine cavity. Retrograde menstruation contributes to the endometrial tissue implantation and the establishment of endometriotic lesions at ectopic sites. It has been suggested that the endometriotic lesions are rich in angiogenic growth factors, while they have an essential role in survival and invasion of these cells. We investigated regulation of microRNA-93 (miR-93) and its involvement with vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase (MMP) 3 expression in women with endometriosis.
Materials and Methods: This was a cross-sectional study at Central Surgical Installation, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, between October 2020 and November 2021. Eutopic and ectopic endometrial tissues were collected from 30 subjects with laparoscopically-confirmed endometriotic women. Normal endometrial cells of non-endometriosis women served as controls. Total RNA was isolated from all samples and a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to analyze the expression of miR-93, VEGFA and MMP3.
Results: There was no significant difference in the expression levels of VEGFA (2.14 ± 0.50, P=0.719) and MMP3 (2.99 ± 0.42, P=0.583) between endometriotic lesions of endometriosis women and the healthy endometrium. Expression of miR-93 was significantly lower in the eutopic endometrium (16.7 fold) and ectopic endometriotic lesion (20 fold) compared to the normal endometrium (P<0.001). Furthermore, we also observed a significant correlation between miR-93 and VEGFA expression in eutopic endometrium obtained from women with endometriosis (r=-0.544, P=0.029). Expression of the miR-93 was also negatively correlated with MMP3 expression in both eutopic (r=-0.412, P=0.01) and ectopic (r=-0.539, P=0.03) endometrial cells of women with endometriosis.
Conclusion: VEGFA and MMP3 expression levels trended to be increased in both eutopic and ectopic endometrial tissues of endometriosis women, while down-regulation of miR-93 might be involved in the alteration of VEGFA and MMP3 in endometriosis.


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