Su Chang-Liang, Deng Tao-Ran, Shang Zhen, Xiao Yi
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie-Fang Avenue, 430030, Wuhan, Hubei, China.
Int J Hematol. 2015 Jul;102(1):76-85. doi: 10.1007/s12185-015-1797-x. Epub 2015 May 5.
It has recently been shown that JARID2 contributes to the malignant character of solid tumors, such as epithelial-mesenchymal transition in lung and colon cancer cell lines, but its role in leukemia progression is unexplored. In this study, we explored the effect and underlying molecular mechanism of JARID2 on leukemia cell proliferation. Real-time PCR and Western assay were carried out to detect JARID2 and CCND1 expression. Cell number and cell cycle change were detected using hemocytometer and flow cytometry, and a ChIP assay was utilized to investigate JARID2 and H3K27me3 enrichment on the CCND1 promoter. JARID2 is down-regulated in B-chronic lymphocytic leukemia (B-CLL) and acute monocytic leukemia (AMOL), and knockdown of JARID2 promotes leukemia cell proliferation via acceleration of the G1/S transition. Conversely, ectopic expression of JARID2 inhibits these malignant phenotypes. Mechanistic studies show that JARID2 negatively regulates CCND1 expression by increasing H3K27 trimethylation on the CCND1 promoter. Our findings indicate that JARID2 is a negative regulator of leukemia cell proliferation, and functions as potential tumor suppressor in leukemia.
最近的研究表明，JARID2与实体瘤的恶性特征有关，如在肺癌和结肠癌细胞系中的上皮-间质转化，但其在白血病进展中的作用尚未得到探索。在本研究中，我们探讨了JARID2对白血病细胞增殖的影响及其潜在分子机制。通过实时PCR和Western检测法检测JARID2和CCND1的表达。使用血细胞计数器和流式细胞术检测细胞数量和细胞周期变化，并利用染色质免疫沉淀实验（ChIP）研究JARID2和H3K27me3在CCND1启动子上的富集情况。JARID2在B细胞慢性淋巴细胞白血病（B-CLL）和急性单核细胞白血病（AMOL）中表达下调，敲低JARID2可通过加速G1/S期转换促进白血病细胞增殖。相反，JARID2的异位表达可抑制这些恶性表型。机制研究表明，JARID2通过增加CCND1启动子上的H3K27三甲基化来负调控CCND1的表达。我们的研究结果表明，JARID2是白血病细胞增殖的负调节因子，在白血病中发挥潜在的肿瘤抑制作用。
