An integrated genomic approach identifies HOXC8 as an upstream regulator in ovarian endometrioma

Purpose: To identify the upstream regulators (URs) involved in the onset and pathogenesis of ovarian endometrioma.

Methods: Recently, a method called SMITE that uses transcriptome data in combination with publicly available data for identifying URs of cellular processes has been developed.  Here, we used SMITE with transcriptome data from ovarian endometrioma stromal cells (ovESCs) and eutopic endometrium stromal cells (euESCs) in combination with publicly available gene regulatory network data.  To confirm the URs identified by SMITE, we developed a Boolean network simulation to see if correcting aberrant expressions of the identified genes could restore the entire gene expression profile of ovESCs to a profile similar to that of euESCs.  We then established euESCs overexpressing the identified gene and characterized them by cell function assays and transcriptome analysis.

Results: SMITE identified 12 potential URs in ovarian endometrioma that were confirmed by the Boolean simula...