Oestrogen promotes the progression of adenomyosis by inhibiting CITED2 through miR-145
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This study investigated how oestrogen drives adenomyosis progression by downregulating CITED2 expression via miR-145.
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Abstract
RESEARCH QUESTION: Is the microRNA miR-145 involved in adenomyosis, and by what mechanisms does it affect disease development and is itself regulated?
DESIGN: Fluorescence in-situ hybridization was used to observe the expression pattern of miR-145 in adenomyosis ectopic endometrium (n = 13), adenomyosis eutopic endometrium (n = 15) and non-adenomyosis eutopic endometrium (n = 14). RNA sequencing was used to screen target genes as well as downstream pathways of miR-145, which were validated by reporter gene assay, quantitative polymerase chain reaction and western blot, and further analysed using cell migration assay and chromatin immunoprecipitation assay.
RESULTS: The fluorescence in-situ hybridization assay revealed a noteworthy elevation in miR-145 expression in adenomyosis tissue compared with non-adenomyosis tissue. Furthermore, RNA sequencing analysis revealed that overexpression of miR-145 resulted in heightened expression of genes associated with the cytokine signalling pathway, nucleotide-binding and oligomerization domain-like pathway and adhesion pathway, including IL-1β and IL-6. Our study has identified CITED2 as a downstream direct target gene of miR-145, which is implicated in the inhibition of stromal cell migration induced by miR-145. Moreover, chromatin immunoprecipitation was used to validate the direct effect of oestradiol on the promoter region of miR-145, mediated by oestrogen receptor α, which facilitates the upregulation of miR-145 expression.
CONCLUSION: Our findings provide evidence supporting the role of oestradiol, acting through its receptor α, in modulating the discovered miR-145-CITED2 signalling axis, thereby promoting the progression of adenomyosis.
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