Variation in MicroRNA Expression Profile of Uterine Leiomyoma with Endometrial Cavity Distortion and Endometrial Cavity Non-Distortion.

Yong Kim,Chang Suh,Yoon Kim,Jung Shin,Hoon Kim,Seung-Yup Ku

doi:10.3390/ijms19092524

Abstract

The expression profile of microRNA (miRNA) in uterine leiomyoma (UL) cells is different from that in normal uterine myometrial (UM) cells. The effect of UL cells on uterine receptivity might vary according to their ability to distort the uterine endometrial cavity. However, the variation in miRNA expression profiles between endometrial cavity-distorting leiomyoma (ECDL) and endometrial cavity non-distorting leiomyoma (ECNDL) cells remains unknown. This study aimed to elucidate whether the expression profile of miRNAs in ECDL cells is dissimilar to that of ECNDL cells in uterus. Pelviscopic myomectomy was performed to obtain tissue samples of UL and their corresponding normal UM tissues (matched) from patients with UL (n = 26), among whom women with ECNDL and ECDL numbered 15 and 11, respectively. The relative expression of hsa-miR-15b, -29a, -29b, -29c, -197, and -200c as well as the candidate target genes in UL cells was compared to those in the matched UM cells using qRT-PCR to assess their ability to cause ECD. The spatial expression of miRNAs and target genes in the UL tissues was analyzed using in situ hybridization. Target gene expression was analyzed using qPCR after transfection with the mimics and inhibitors of miRNAs in UL cells. The relative expression level of miR-15b was upregulated, and the relative expression levels of miR-29a, -29b, -29c, -197, and -200c were downregulated in UL cells compared to those in UM cells. The relative expression levels of progesterone receptor, estrogen receptor, and matrix metalloproteinases (MMPs) were upregulated in UL cells compared to those in UM cells. The relative expression levels of miR-29c and -200c were downregulated, and the relative expression levels of estrogen receptor, MMPs and tissue inhibitors of metalloproteinases (TIMPs) were upregulated in ECDL cells compared to those in ECNDL cells. The expression profile of miRNAs in UL cells varied with respect to the occurrence or absence of endometrial cavity distortion. The biochemical properties of UL might be regulated by miRNAs in order to alter their effect on structural homeostasis of the uterus.

Highlights

Uterine leiomyomas (ULs) are the most common benign tumors of the female reproductive tract in humans [1]
This study aimed to evaluate the variation between the miRNA expression profiles in UL tissues of patients with endometrial cavity distortion (ECD) and endometrial cavity non-distortion (ECND) using uterine myometrium (UM) tissues as matched controls
Significant variations in patient characteristics such as age, UL size, and main symptoms were not observed between the subjects with endometrial cavity-distorting leiomyoma (ECDL) and endometrial cavity non-distorting leiomyoma (ECNDL) (Table 1)

Summary

Introduction

Uterine leiomyomas (ULs) are the most common benign tumors of the female reproductive tract in humans [1]. ULs that cause anatomical disruption of the normal uterine endometrial structure might affect the implantation and development of embryos [3,4]. A few studies reported an improvement in the pregnancy outcome after surgically treating ULs with endometrial cavity distortion (ECD) using myomectomy [5,6]. Several recent studies implicated the potential regulatory functions of a few specific miRNAs in order to elucidate the pathogenesis of UL. These studies compared the expression levels of specific miRNAs in uterine myometrium (UM) and UL tissues [17–19]. The variation in miRNA expression profile of UL tissue according to accompanying ECD remains unknown, its clinical implication could be significant

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