Targeting P16INK4A in uterine serous carcinoma through inhibition of histone demethylation.

Targeting P16INK4A in uterine serous carcinoma through inhibition of histone demethylation. Oncol Rep. 2019 Mar 14;: Authors: Xiao Z, He Y, Liu C, Xiang L, Yi J, Wang M, Shen T, Shen L, Xue Y, Shi H, Liu P Abstract Uterine serous carcinoma (USC) is a subtype of endometrial cancer. Compared with endometrial endometroid carcinoma, the majority of USC cases are more aggressive. Cyclin-dependent kinase inhibitor 2A (P16INK4A) is a canonical tumor suppressor that blocks cell cycle progression; however, P16INK4A is overexpressed in USC. The aim of the present study was to determine the role of P16INK4A in P16INK4A‑positive endometrial cancer, with the hope of elucidating a novel therapeutic approach for this type of malignancy. A total of 2 endometrial cancer cell lines, ETN‑1 and EFE‑184, were selected for further investigation, due to them being known to express high levels of P16INK4A. Using short hairpin RNA targeting P16INK4A, P16INK4A was downregulated in these cancer cell lines. Cell viability and migration were examined via 2D/3D clonogenic and wound healing assays. Subsequently, GSK‑J4, a histone demethylase inhibitor, was employed to deplete P16INK4A in these cancer cell lines and an ex vivo culture system of a patient‑derived xenograft (PDX) endometrial tumor sample. Following P16INK4A knockdown, the proliferation and migration of ETN‑1 and EFE‑184 cells markedly declined. When exposed to GSK‑J4, the levels of KD...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research