miR-10a inhibits cell proliferation and promotes cell apoptosis by targeting BCL6 in diffuse large B-cell lymphoma

被引:43
作者
Fan, Qian [1 ]
Meng, Xiangrui [1 ]
Liang, Hongwei [2 ]
Zhang, Huilai [1 ]
Liu, Xianming [1 ]
Li, Lanfang [1 ]
Li, Wei [1 ]
Sun, Wu [3 ]
Zhang, Haiyang [3 ]
Zen, Ke [2 ]
Zhang, Chen-Yu [2 ]
Zhou, Zhen [2 ]
Chen, Xi [2 ]
Ba, Yi [3 ]
机构
[1] Tianjin Med Univ, Canc Inst & Hosp, SinoUS Ctr Lymphoma & Leukemia, Dept Lymphoma,Natl Clin Res Ctr Canc,Key Lab Canc, Tianjin 300060, Peoples R China
[2] Nanjing Univ, NJU Adv Inst Life Sci, Sch Life Sci,State Key Lab Pharmaceut Biotechnol, Jiangsu Engn Res Ctr MicroRNA Biol & Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
[3] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Dept Digest,Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China
关键词
microRNA; miR-10a; BCL6; DLBCL; proliferation; apoptosis; HUMAN CANCER; MICRORNA SIGNATURES; DOWN-REGULATION; RETINOIC ACID; MECHANISMS; EXPRESSION; DIFFERENTIATION; BIOGENESIS; MOUSE;
D O I
10.1007/s13238-016-0316-z
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The BCL6 (B-Cell Lymphoma 6) gene is a proto-oncogene that is often expressed in diffuse large B-cell lymphomas (DLBCLs). BCL6 loss of function can kill DLBCL cells, demonstrating that BCL6 is necessary for the survival of DLBCL cells and could be a therapeutic target. In this study, we found that BCL6 protein levels were consistently upregulated in DLBCL tissues, whereas its mRNA levels varied randomly in tissues, suggesting that a post-transcriptional mechanism was involved in BCL6 regulation. We used bioinformatics analysis to search for miRNAs, which potentially target BCL6, and identified specific targeting sites for miR-10a in the 3'-untranslated region (3'-UTR) of BCL6. We further identified an inverse correlation between miR-10a levels and BCL6 protein levels, but not mRNA levels, in DLBCL tumor tissue samples. By overexpressing or knocking down miR-10a in DLBCL cells, we experimentally validated that miR-10a directly recognizes the 3'-UTR of the BCL6 transcript and regulated BCL6 expression. Furthermore, we demonstrated that negatively regulating BCL6 by miR-10a suppressed the proliferation and promoted apoptosis of DLBCL cells.
引用
收藏
页码:899 / 912
页数:14
相关论文
共 44 条
[1]   Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth [J].
Agirre, Xabier ;
Jimenez-Velasco, Antonio ;
San Jose-Eneriz, Edurne ;
Garate, Leire ;
Bandres, Eva ;
Cordeu, Lucia ;
Aparicio, Oscar ;
Saez, Borja ;
Navarro, German ;
Vilas-Zornoza, Amaia ;
Perez-Roger, Ignacio ;
Garcia-Foncillas, Jesus ;
Torres, Antonio ;
Heiniger, Anabel ;
Jose Calasanz, Maria ;
Fortes, Puri ;
Roman-Gomez, Jose ;
Prosper, Felipe .
MOLECULAR CANCER RESEARCH, 2008, 6 (12) :1830-1840
[2]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[3]   The human BCL6 transgene promotes the development of lymphomas in the mouse [J].
Baron, BW ;
Anastasi, J ;
Montag, A ;
Huo, DZ ;
Baron, RM ;
Karrison, T ;
Thirman, MJ ;
Subudhi, SK ;
Chin, RK ;
Felsher, DW ;
Fu, YX ;
McKeithan, TW ;
Baron, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (39) :14198-14203
[4]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[5]   Roles of BCL6 in normal and transformed germinal center B cells [J].
Basso, Katia ;
Dalla-Favera, Riccardo .
IMMUNOLOGICAL REVIEWS, 2012, 247 :172-183
[6]   LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas [J].
Bertolo, Cristina ;
Roa, Sergio ;
Sagardoy, Ainara ;
Mena-Varas, Maria ;
Robles, Eloy F. ;
Martinez-Ferrandis, Jose I. ;
Sagaert, Xavier ;
Tousseyn, Thomas ;
Orta, Alberto ;
Lossos, Izidore S. ;
Amar, Salomon ;
Natkunam, Yasodha ;
Briones, Javier ;
Melnick, Ari ;
Malumbres, Raquel ;
Martinez-Climent, Jose A. .
BRITISH JOURNAL OF HAEMATOLOGY, 2013, 162 (05) :621-630
[7]   MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[8]   Targeting BCL6 in diffuse large B-cell lymphoma: what does this mean for the future treatment? [J].
Cerchietti, Leandro ;
Melnick, Ari .
EXPERT REVIEW OF HEMATOLOGY, 2013, 6 (04) :343-345
[9]   Role of miR-143 targeting KRAS in colorectal tumorigenesis [J].
Chen, X. ;
Guo, X. ;
Zhang, H. ;
Xiang, Y. ;
Chen, J. ;
Yin, Y. ;
Cai, X. ;
Wang, K. ;
Wang, G. ;
Ba, Y. ;
Zhu, L. ;
Wang, J. ;
Yang, R. ;
Zhang, Y. ;
Ren, Z. ;
Zen, K. ;
Zhang, J. ;
Zhang, C-Y .
ONCOGENE, 2009, 28 (10) :1385-1392
[10]   BCL6 - regulated by AhR/ARNT and wild-type MEF2B - drives expression of germinal center markers MYBL1 and LMO2 [J].
Ding, Jie ;
Dirks, Wilhelm G. ;
Ehrentraut, Stefan ;
Geffers, Robert ;
MacLeod, Roderick A. F. ;
Nagel, Stefan ;
Pommerenke, Claudia ;
Romani, Julia ;
Scherr, Michaela ;
Vaas, Lea A. I. ;
Zaborski, Margarete ;
Drexler, Hans G. ;
Quentmeier, Hilmar .
HAEMATOLOGICA, 2015, 100 (06) :801-809