LncRNA NR-104098 Inhibits AML Proliferation and Induces Differentiation Through Repressing EZH2 Transcription by Interacting With E2F1

Yubin Feng; Shuang Hu; Lanlan Li; Shengpeng Zhang; Jikang Liu; Xiaoling Xu; Meiju Zhang; Tianxi Du; Yan Du; Xiaoqing Peng; Feihu Chen

doi:10.3389/fcell.2020.00142

LncRNA NR-104098 Inhibits AML Proliferation and Induces Differentiation Through Repressing EZH2 Transcription by Interacting With E2F1

Front Cell Dev Biol. 2020 Mar 26:8:142. doi: 10.3389/fcell.2020.00142. eCollection 2020.

Authors

Yubin Feng^{1

2}, Shuang Hu^{1

2}, Lanlan Li^{1

2}, Shengpeng Zhang³, Jikang Liu^{1

2}, Xiaoling Xu^{1

2}, Meiju Zhang^{1

2}, Tianxi Du^{1

2}, Yan Du^{1

2}, Xiaoqing Peng^{1

2}, Feihu Chen^{1

2}

Affiliations

¹ The Key Laboratory of Major Autoimmune Diseases of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.
² The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Hefei, China.
³ School of Pharmacy, Wannan Medical College, Wuhu, China.

Abstract

Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Most lncRNAs have been proven to have biological and clinical significance in acute myeloid leukemia (AML), but further investigation remains necessary. In this study, we investigated lncRNA NR-104098 in AML and its specific mechanism. The microarray analysis was performed on NB4 cells. Based on the related analysis results, we identified that lncRNA NR-104098 is a suppressor gene that is significantly upregulated in AML cells. LncRNA NR-104098 could inhibit proliferation and induce differentiation in AML cells in vitro and also play main role in the mouse xenografts. Mechanically, it was confirmed that lncRNA NR-104098 may effectively inhibit EZH2 transcription by directly binding to E2F1 and recruiting E2F1 to the EZH2 promoter. In addition, ATPR can significantly increase the expression of lncRNA NR-104098, whereas knocking down NR104098 can inhibit the inhibitory effect of ATPR on the proliferation and induction differentiation of AML cells. Taken together, these results lead to deeper insight into the mechanism of ATPR-induced AML differentiation and prevent proliferation by inhibiting EZH2 on the transcriptional level.

Keywords: E2F1; EZH2; NR-104098; acute myeloid leukemia (AML); differentiation; long non-coding RNAs; proliferation.