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

• DOI: 10.1038/s41419-021-03637-4
• Publication Date: 2021-05-03T14:43:34Z
• Authors: Haiping Song; Lijuan Chen; Wei Liu; Xiaoli Xu; Yongming Zhou; Jianhua Zhu; Xuexing Chen; Ziping Li; Hao Zhou
• Keywords: DNA (Cytosine-5-)-Methyltransferase 1; Male; 0301 basic medicine; QH573-671; PTEN Phosphohydrolase; DNA Methylation; Transfection; Article; Mice; 03 medical and health sciences; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Animals; Humans; RNA, Long Noncoding; Cytology; Promoter Regions, Genetic

AbstractLong 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.