MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma.
Emerging evidence shows that microRNAs (miRNAs) act as critical regulators in the progression and chemoresistance of multiple tumors, including osteosarcoma (OS). In this study, we found that the level of miR-24 was increased in OS patients' serum, tumor tissues and OS cell lines. Furthermore, we found that knockdown of miR-24 by its specific inhibitors significantly increased the therapeutic effect of doxorubicin (DOX) on OS cell lines (MG-63 and HOS). Moreover, miR-24 inhibitors resensitized the doxorubicin-resistant MG-63 cells (MG-63/R) and HOS cells (HOS/R) to DOX. As the gene of Bcl-2 interacting mediator of cell death (BIM) was proved to be a target of miR-24 in MG-63/R cells, we further observed that the miR-24 inhibitors promoted the DOX-induced apoptosis via mitochondrial pathway. In addition, results of immunoprecipitation showed the release of second mitochondria derived activator of caspase/ direct IAP binding protein with low pI (Smac/DIABLO) abolished the biological activity of X-linked inhibitor of apoptosis protein (XIAP) by binding with it, which subsequently induced the activation of caspase 9, 7 and 3. In summary, those results strongly suggest that the miR-24-BIM-Smac/DIABLO axis might be a novel target for the treatment of OS.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Yangbai
Y
Sun
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Nengbin
N
He
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Yang
Y
Dong
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Chaoyin
C
Jiang
Cell. 2000 Jul 7;102(1):43-53
10929712
Mol Cell Biochem. 2005 May;273(1-2):25-32
16013437
PLoS One. 2015 Apr 15;10 (4):e0123341
25875815
Leukemia. 2012 Sep;26(9):2032-8
22453662
Cancer Res. 2012 Apr 1;72(7):1865-77
22350417
Tumour Biol. 2015 Sep;36(9):7185-94
25894378
Nat Rev Genet. 2007 Feb;8(2):93-103
17230196
Oncol Rep. 2015 Jul;34(1):368-74
25997995
Genes Dev. 2001 Jun 15;15(12 ):1481-6
11410528
Tumour Biol. 2014 Nov;35(11):10731-6
25073511
Methods. 2001 Dec;25(4):402-8
11846609
Cell Rep. 2013 Oct 31;5(2):409-20
24120870
Science. 2001 Apr 27;292(5517):727-30
11326099
Cell. 2003 Jun 13;113(6):673-6
12809598
Cell Physiol Biochem. 2015 ;35(4):1527-36
25791936
Sci Rep. 2015 May 06;5:10120
25944566
Cancer Genet. 2011 Mar;204(3):138-46
21504713
Oncogene. 2014 Feb 27;33(9):1181-9
23474761
J Ovarian Res. 2015 Jun 12;8:36
26063499
Cancer. 2013 Jul 15;119(14):2645-53
23625626
Oncology. 2013;85(5):312-6
24217400
Med Oncol. 2012 Dec;29(5):3190-7
22782668
Nat Rev Cancer. 2006 Apr;6(4):259-69
16557279
World J Stem Cells. 2014 Nov 26;6(5):591-7
25426255
J Cell Sci. 2013 Mar 15;126(Pt 6):1440-53
23418360
Mol Cell. 2010 Feb 12;37(3):299-310
20159550
Exp Oncol. 2012 Oct;34(3):200-11
23070005
Cell. 2000 Jul 7;102(1):33-42
10929711
Mol Cancer Ther. 2008 Nov;7(11):3461-9
19001431
J Biol Chem. 2011 Dec 9;286(49):42292-302
22009755
Cancer Discov. 2011 Sep;1(4):352-65
22145099
Tumour Biol. 2014 Oct;35(10):10213-21
25027405
Biochem Biophys Res Commun. 2003 May 9;304(3):499-504
12729584
Curr Opin Cell Biol. 2010 Dec;22(6):872-81
20888210
Carcinogenesis. 2015 Aug;36(8):894-903
26026166
CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29
24399786
PLoS One. 2014 Apr 30;9(4):e96220
24788441
Oncogene. 2006 Aug 7;25(34):4798-811
16892092
Mol Cell Biochem. 2006 Oct;291(1-2):139-44
16909308