ASH2L is involved in promotion of endometrial cancer progression via upregulation of PAX2 transcription

Absent, small or homeotic 2-like protein (ASH2L) is a core component of multimeric histone methyltransferase complex, which is involved in maintenance of active transcription, participating in several cancers. However, the biological function and molecular mechanism of ASH2L in endometrial cancer (ECa) is largely unknown. Endometrial cancer is one of the common female malignant tumors and the incidence is on the rise. Estrogen-ERalpha signaling as an oncogenic pathway, plays a crucial role in endometrial carcinogenesis. Thus, further exploring the molecular mechanism around ERalpha-mediated gene transcription in ECa would be helpful to understand the tumor development and to find a new therapeutic target for ECa. Here, our study demonstrated that ASH2L was highly expressed in ECa samples, and the higher expression of ASH2L was positively correlated with the poor prognosis. Moreover, we identified that ASH2L associated with ERalpha and knockdown of ASH2L resulted in decreased expression of a subset of the estrogen-induced target genes, including paired box 2 (PAX2), an oncogenic gene in ECa. ASH2L was recruited to cis-regulatory elements at PAX2, thereby altering histone H3K4me3 and H3K27me3 levels, to enhance ERalpha-mediated transactivation. Finally, depletion of ASH2L suppressed endometrial cancer cell proliferation and migration. Our findings suggest that ASH2L participates in promotion of ECa progression, if not all, at least partially via upregulation of PAX2 transcription.