Unraveling the Molecular Landscape of Uterine Fibroids, Insights into HMGA2 and Stem Cell Involvement
Uterine fibroids are prevalent benign tumors in women that exhibit considerable heterogeneity in clinical presentation and molecular characteristics, necessitating a deeper understanding of their etiology and pathogenesis. HMGA2 overexpression has been associated with fibroid development, yet its precise role remains elusive. Mutations in fibroids are mutually exclusive and largely clonal, suggesting that tumors originate from a single mutant cell. We explored a possible role for HMGA2 overexpression in differentiated myometrial cells, hypothesizing its potential to induce a stem cell-like or dedifferentiating phenotype and drive fibroid development. Myometrial cells were immortalized and transduced with an HMGA2 lentivirus to produce HMGA2hi cells. In vitro stem cell assays were conducted and RNA from HMGA2hi and control cells and fibroid-free myometrial and HMGA2 fibroid (HMGA2F) tissues were submitted for RNA-sequencing. HMGA2hi cells have enhanced self-renewal capacity, decreased p