Title:The Acetyltransferase KAT5 Inhibitor NU 9056 Promotes Apoptosis and Inhibits JAK2/STAT3 Pathway in Extranodal NK/T Cell Lymphoma
Volume: 22
Issue: 8
Author(s): Linyan Xu, Yuanyuan Qin, Mengdi Liu, Jun Jiao, Dongyun Tu, Meng Zhang, Dongmei Yan, Xuguang Song, Cai Sun, Feng Zhu, Xiangmin Wang, Wei Sang*Kailin Xu*
Affiliation:
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital
of Xuzhou Medical University, Xuzhou, Jiangsu, China
- Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu, China
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Hematology, The Affiliated Hospital
of Xuzhou Medical University, Xuzhou, Jiangsu, China
- Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu, China
Keywords:
NU 9056, ENKTL, KAT5, apoptosis, JAK2/STAT3, MAPK.
Abstract:
Background: Extranodal natural killer/T cell lymphoma (ENKTL) is an aggressive malignant non-
Hodgkin's lymphoma (NHL) with a poor prognosis. Therefore, novel therapeutic biomarkers and agents must be identified
for the same. KAT5 inhibitor, NU 9056, is a small molecule that can inhibit cellular proliferation; however, its role
in ENKTL has not been studied.
Objective: The present study investigated the effect of NU 9056 in ENKTL cells and explored the possible molecular
mechanism for its antitumour effect.
Methods: The role of NU 9056 in ENKTL cells was investigated through the Cell Counting Kit-8 assay, flow cytometry,
Western blot, and real-time quantitative polymerase chain reaction assay.
Results: NU 9056 inhibited ENKTL cell proliferation and induced G2/M phase arrest. NU 9056 also induced apoptosis
by upregulating DR4, DR5, and caspase 8 expressions. Additionally, NU 9056 increased the expression of Bax,
Bid, and cytochrome C and decreased the expression of Bcl-2, Mcl-1, and XIAP. Furthermore, NU 9056 activated
endoplasmic reticulum (ER) stress and inhibited the JAK2/STAT3 signalling pathway. The p38 mitogen-activated
protein kinase (MAPK) signalling pathway was also activated by NU 9056, and the ERK signalling pathway was suppressed
in natural killer/T cell lymphoma cells.
Conclusion: NU 9056 inhibited cell proliferation, arrested cell cycle in the G2/M phase, and induced apoptosis through
the stimulation of ER stress, thus inhibiting the JAK2/STAT3 signalling pathway and regulating MAPK pathways in
ENKTL cells.
