miR-150 inhibits terminal erythroid proliferation and differentiation

// Zhiwei Sun 1 , Ye Wang 1 , Xu Han 1 , Xielan Zhao 2 , Yuanliang Peng 1 , Yusheng Li 2 , Minyuan Peng 2 , Jianhui Song 2 , Kunlu Wu 1 , Shumin Sun 1 , Weihua Zhou 1 , Biwei Qi 1 , Chufan Zhou 1 , Huiyong Chen 1 , Xiuli An 3, 4 , Jing Liu 1 1 The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha 410078, China 2 Xiangya Hospital, Central South University, Changsha 410008, China 3 College of Life Sciences, Zhengzhou University, Zhengzhou 450001, China 4 Laboratory of Membrane Biology, New York Blood Center, New York, NY 10065, USA Correspondence to: Jing Liu, e-mail: liujing2@sklmg.edu.cn Xiuli An, e-mail: xan@nybloodcenter.org Huiyong Chen, e-mail: chenhy5000@126.com Keywords: miR-150, terminal erythropoiesis, 4.1R, erythroid proliferation, transcriptional profiling Received: May 15, 2015      Accepted: October 22, 2015      Published: November 03, 2015 ABSTRACT MicroRNAs (miRNAs), a class of small non-coding linear RNAs, have been shown to play a crucial role in erythropoiesis. To evaluate the indispensable role of constant suppression of miR-150 during terminal erythropoiesis, we performed miR-150 gain- and loss-of-function experiments on hemin-induced K562 cells and EPO-induced human CD34 + cells. We found that forced expression of miR-150 suppresses commitment of hemoglobinization and CD235a labeling in both cell types. Erythroid proliferation is also inhibited via inducing apoptosis and blocking the cell cycle when miR-150 is overexpressed. In contrast, miR-150 inhibition promotes terminal erythropoiesis. 4.1 R gene is a new target of miR-150 during terminal erythropoiesis, and its abundance ensures the mechanical stability and deformability of the membrane. However, knockdown of 4.1 R did not affect terminal erythropoiesis. Transcriptional profiling identified more molecules involved in terminal erythroid dysregulation derived from miR-150 overexpression. These results shed light on the role of miR-150 during human terminal erythropoiesis. This is the first report highlighting the relationship between miRNA and membrane protein and enhancing our understanding of how miRNA works in the hematopoietic system.