miR-10a inhibits cell proliferation and promotes cell apoptosis by targeting BCL6 in diffuse large B-cell lymphoma.
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.
Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Qian
Q
Fan
Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Xiangrui
X
Meng
State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
Hongwei
H
Liang
Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Huilai
H
Zhang
Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Xianming
X
Liu
Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Lanfang
L
Li
Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Wei
W
Li
Department of Digestion, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Wu
W
Sun
Department of Digestion, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Haiyang
H
Zhang
State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
Ke
K
Zen
State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.
Chen-Yu
CY
Zhang
State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China. zhenzhou@nju.edu.cn.
Zhen
Z
Zhou
State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China. xichen@nju.edu.cn.
Xi
X
Chen
Department of Digestion, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China. bayi@tjmuch.com.
Yi
Y
Ba
D020413:3' Untranslated Regions; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000096:biosynthesis* / Q000235:genetics
D020413:3' Untranslated Regions; C084103:BCL6 protein, human; C000715470:MAS1 protein, human; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6
BCL6; DLBCL; apoptosis; miR-10a; microRNA; proliferation