MiR-144 Regulates Hemoglobin Expression in Human Erythroid Cell Line


  • Tipparat PENGLONG Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
  • Apisara SAENSUWANNA Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
  • Jitpanu KOCHAROENWAT Faculty of Medical Technology, Prince of Songkla University, Songkhla 90110, Thailand
  • Wittawat BOORINTARAGOT Faculty of Medical Technology, Prince of Songkla University, Songkhla 90110, Thailand
  • Suppanut FUPONGSIRIPHAN Faculty of Medical Technology, Prince of Songkla University, Songkhla 90110, Thailand
  • Kanitta SRINOUN Faculty of Medical Technology, Prince of Songkla University, Songkhla 90110, Thailand




MiR-144, ɑ-globin, z-globin


The regulation of globin gene expression is significantly important to understand the pathogenesis of globin gene disorders. Recent findings have shown that microRNAs (miRNAs, miRs) play an important role in the regulation of globin gene expression. The miR-144 is an erythroid lineage-specific miRNA, in which its expression mediates NRF2 gene silencing and inhibits fetal hemoglobin expression. However, roles of miR-144 to other globin genes expression especially in ɑ-globin cluster remain unknown. This study, thus, examined the functional studies of miR-144 to globin gene expression in K562 human erythroid cell line. The results revealed that ɑ-globin and z-globin gene expression were silenced by the overexpressed miR-144 and that correlated with the reduced expression of KLF1- the suspected target gene. By contrast, transfection with miR-144 inhibitor reversed the silencing effect of miR-144. On the other hand, miR-144 had no effect to β-globin gene expression. Our results sustain the findings of the previous studies that the overexpression of miR-144 correlates with the repressing of NRF2 and 𝛄-globin gene expression. Taken together, our results suggest that miR-144 plays a key role in globin gene expression by silencing 𝛄-globin through NRF2 target mRNA and repressing adult ɑ-globin and embryonic z-globin gene expression possibly by targeting KLF1 gene.


Download data is not yet available.


Metrics Loading ...


DR Higgs, MA Vickers, AO Wilkie, IM Pretorius, AP Jarman, DJ Weatherall. A review of the molecular genetics of the human alpha-globin gene cluster. Blood 1989; 73, 1081-104.

T Maniatis, EF Fritsch, J Lauer and RM Lawn. The molecular genetics of human hemoglobins. Annu. Rev. Genet. 1980; 14, 145-78.

G Stamatoyannopoulos. Control of globin gene expression during development and erythroid differentiation. Exp. Hematol. 2005; 33, 259-71.

DR Higgs, D Garrick, E Anguita, MD Gobbi, J Hughes, M Muers, D Vernimmen, K Lower, M Law, A Argentaro, MA Deville and R Gibbons. Understanding alpha-globin gene regulation: Aiming to improve the management of thalassemia. Ann. N. Y. Acad. Sci. 2005; 1054, 92-102.

D Zhou, K Liu, CW Sun, KM Pawlik and TM Townes. KLF1 regulates BCL11A expression and gamma- to beta-globin gene switching. Nat. Genet. 2010; 42, 742-4.

D Donze, TM Townes and JJ Bieker. Role of erythroid Kruppel-like factor in human gamma- to beta-globin gene switching. J. Biol. Chem. 1995; 270, 1955-9.

J Xu, VG Sankaran, M Ni, TF Menne, RV Puram, W Kim and SH Orkin. Transcriptional silencing of {gamma}-globin by BCL11A involves long-range interactions and cooperation with SOX6. Genes Dev. 2010; 24, 783-98.

J Xu, DE Bauer, MA Kerenyi, TD Vo, S Hou, YJ Hsu, H Yao, JJ Trowbridge, G Mandel and SH Orkin. Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A. Proc. Natl. Acad. Sci. USA 2013; 110, 6518-23.

M Roosjen, B McColl, B Kao, LJ Gearing, ME Blewitt and J Vadolas. Transcriptional regulators Myb and BCL11A interplay with DNA methyltransferase 1 in developmental silencing of embryonic and fetal beta-like globin genes. FASEB J. 2014; 28, 1610-20.

B Li, X Zhu, CM Ward, A Starlard-Davenport, M Takezaki, A Berry, A Ward, C Wilder, C Neunert, A Kutlar and BS Pace. MIR-144-mediated NRF2 gene silencing inhibits fetal hemoglobin expression in sickle cell disease. Exp. Hematol. 2019; 70, 85-96.

DP Bartel. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004; 116, 281-97.

I Azzouzi, H Moest, J Winkler, JC Fauchère, AP Gerber, B Wollscheid, M Stoffel, M Schmugge and O Speer. MicroRNA-96 directly inhibits gamma-globin expression in human erythropoiesis. PLoS One 2011; 6, e22838.

YT Lee, JF de Vasconcellos, J Yuan, C Byrnes, SJ Noh, ER Meier, KS Kim, A Rabel, M Kaushal, SA Muljo and JL Miller. LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo. Blood 2013; 122, 1034-41.

VG Sankaran, TF Menne, D Scepanovic, JA Vergilio, P Ji, J Kim, P Thiru, SH Orkin, ES Lander and HF Lodish. MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13. Proc. Natl. Acad. Sci. USA 2011; 108, 1519-24.

V Lulli, P Romania, O Morsilli, P Cianciulli, M Gabbianelli, U Testa, A Giuliani and G Marziali. MicroRNA-486-3p regulates gamma-globin expression in human erythroid cells by directly modulating BCL11A. PLoS One 2013; 8, e60436.

CM Ward, B Li and BS Pace. Stable expression of miR-34a mediates fetal hemoglobin induction in K562 cells. Exp. Biol. Med. (Maywood) 2016; 241, 719-29.

Y Li, D Liu, X Zhang, Z Li, Y Ye, Q Liu, J Shen, Z Chen, H Huang, Y Liang, X Han, J Liu, X Ang, N Mohandas and X Xu. miR-326 regulates HbF synthesis by targeting EKLF in human erythroid cells. Exp. Hematol. 2018; 63, 33-40.

YF Fu, TT Du, M Dong, KY Zhu, CB Jing, Y Zhang, L Wang, HB Fan, Y Chen, Y Jin, GP Yue, SJ Chen, Z Chen, QH Huang, Q Jing, M Deng and TX Liu. Mir-144 selectively regulates embryonic alpha-hemoglobin synthesis during primitive erythropoiesis. Blood 2009; 113, 1340-9.

J Xu, C Peng, VG Sankaran, Z Shao, EB Esrick, BG Chong, GC Ippolito, Y Fujiwara, BL Ebert, PW Tucker and SH Orkin. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science 2011; 334, 993-6.

F Jiang, YX Qu, GL Chen, J Li, JY Zhou, LD Zuo, C Liao and DZ Li. KFL1 gene variants in alpha-thalassemia individuals with increased fetal hemoglobin in a Chinese population. Hemoglobin 2018; 42, 161-5.

AC Oates, SJ Pratt, B Vail, Y Yl, RK Ho, SL Johnson, JH Postlethwait and LI Zon. The zebrafish klf gene family. Blood 2001; 98, 1792-801.

P Basu, TK Lung, W Lemsaddek, TG Sargent, DCJ Williams, M Basu, LC Redmond, JB Lingrel, JL Haar and JA Lloyd. EKLF and KLF2 have compensatory roles in embryonic beta-globin gene expression and primitive erythropoiesis. Blood 2007; 110: 3417-25.




How to Cite

PENGLONG, T. ., SAENSUWANNA, A. ., KOCHAROENWAT, J. ., BOORINTARAGOT, W. ., FUPONGSIRIPHAN, S. ., & SRINOUN, K. . (2020). MiR-144 Regulates Hemoglobin Expression in Human Erythroid Cell Line. Walailak Journal of Science and Technology (WJST), 17(11), 1221–1229. https://doi.org/10.48048/wjst.2020.10712