Depleting long noncoding RNA HOTAIR attenuates chronic myelocytic leukemia progression by binding to DNA methyltransferase 1 and inhibiting PTEN gene promoter methylation

被引:30
作者
Song, Haiping [1 ]
Chen, Lijuan [2 ]
Liu, Wei [3 ]
Xu, Xiaoli [4 ]
Zhou, Yongming [5 ]
Zhu, Jianhua [6 ]
Chen, Xuexing [3 ]
Li, Ziping [3 ]
Zhou, Hao [3 ]
机构
[1] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Breast & Thyroid Surg Ctr, Wuhan, Peoples R China
[2] Huazhong Univ Sci & Technol, Union Hosp, Dept Obstet & Gynecol, Tongji Med Coll, Wuhan, Peoples R China
[3] Huazhong Univ Sci & Technol, Inst Hematol, Union Hosp, Tongji Med Coll, Wuhan, Peoples R China
[4] Foshan 1 Peoples Hosp, Dept Hematol, Fosan, Peoples R China
[5] Wuhan Univ Sci & Technol, Affiliated Tianyou Hosp, Dept Hematol, Wuhan, Peoples R China
[6] Huazhong Univ Sci & Technol, Wuhan Hosp 1, Tongji Med Coll, Clin Immunol Lab, Wuhan, Peoples R China
基金
中国国家自然科学基金;
关键词
MYELOID-LEUKEMIA; BETA-CATENIN; EXPRESSION; CELLS; PROLIFERATION;
D O I
10.1038/s41419-021-03637-4
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Long noncoding RNAs (lncRNAs) are known to play a key role in chronic myelocytic leukemia (CML) development, and we aimed to identify the involvement of the lncRNA HOX antisense intergenic RNA (HOTAIR) in CML via binding to DNA methyltransferase 1 (DNMT1) to accelerate methylation of the phosphatase and tensin homolog (PTEN) gene promoter. Bone marrow samples from CML patients and normal bone marrow samples from healthy controls were collected. HOTAIR, DNMT1, DNMT3A, DNMT3B, and PTEN expression was detected. The biological characteristics of CML cells were detected. The relationship among HOTAIR, DNMT1, and PTEN was verified. Tumor volume and weight in mice injected with CML cells were tested. We found that HOTAIR and DNMT1 expression was increased and PTEN expression was decreased in CML. We also investigated whether downregulated HOTAIR or DNMT1 reduced proliferation, colony formation, invasion, and migration and increased the apoptosis rate of CML cells. Moreover, we tested whether low expression of HOTAIR or DNMT1 reduced the volume and weight of tumors in mice with CML. Collectively, the results of this studied showed that depleted HOTAIR demonstrated reduced binding to DNMT1 to suppress CML progression, which may be related to methylation of the PTEN promoter.
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页数:11
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