JARID2 inhibits leukemia cell proliferation by regulating CCND1 expression.
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.
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie-Fang Avenue, 430030, Wuhan, Hubei, China.
Chang-Liang
CL
Su
Tao-Ran
TR
Deng
Zhen
Z
Shang
Yi
Y
Xiao
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D019938:Cyclin D1 / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D064593:Heterografts; D006657:Histones / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden; D055815:Young Adult
D006657:Histones; C547777:JARID2 protein, human; D019938:Cyclin D1; D063151:Polycomb Repressive Complex 2