MicroRNA signature and regulatory functions in the endometrium during normal and disease states

Abstract

During the menstrual cycle, human endometrium undergoes extensive cyclic morphologic and biochemical modifications in preparation for embryo implantation. These processes are highly regulated by ovarian steroids and various locally expressed gene products and involve inflammatory reaction, apoptosis, cell proliferation, angiogenesis, differentiation (tissue formation), and tissue remodeling. MicroRNAs (miRNAs) have emerged as key regulators of gene expression, and their altered and/or aberrant expression has been associated with establishment and progression of various disorders, including tumorigenesis. This review highlights the endometrial expression of miRNAs and their potential regulatory functions under normal and pathologic conditions such as endometriosis, dysfunctional uterine bleeding, and endometrial cancer. Given the key regulatory function of miRNAs on gene expression stability, understanding the underlying mechanisms of how endometrial miRNAs are regulated and identifying their specific target genes and their functions might lead to the development of preventive and therapeutic strategies by regulating specific target genes associated with such reproductive disorders.

Figure 1

Schematic representation of miRNAs potential regulatory function on endometrial gene expression whose products are involved in regulating various cellular activities such as inflammatory and immune response, apoptosis, angiogenesis, cell growth and differentiation, and so forth. These cellular activities are critical components of the endometrial degradative and regenerative processes during the menstrual cycle and are consistent throughout the reproductive years.

Figure 2

The aberrant endometrial expression of these miRNAs due to oncogenic/tumor suppressor gene products resulting in altered expression of their target genes that regulate inflammatory and immune response, apoptosis, angiogenesis, cell growth and differentiation, or cellular transformation may lead to dysfunctional uterine bleeding, embryo implantation defect, endometriosis, and endometrial cancers. Whether altered expression of miRNAs results in establishment of these disorders or their altered expression is the consequence of disorders, such as endometriosis, thus modulating the stability of their specific target genes remains to be investigated.