MicroRNA-297b-5p/3p target Mllt3/Af9 to suppress lymphoma cell proliferation, migration and invasion in vitro and tumor growth in nude mice

MicroRNA-297b-5p/3p target Mllt3/Af9 to suppress lymphoma cell proliferation, migration and invasion in vitro and tumor growth in nude mice
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MicroRNA-297b-5p/3p靶向Mllt3/Af9抑制淋巴瘤细胞体外增殖、迁移和侵袭以及裸鼠肿瘤生长

DOI:
10.3109/10428194.2012.678005
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发表时间:
2012-03
期刊:
Leuk Lymphoma
影响因子:
--
通讯作者:
杨云青 (Yang, J.Y.)
杨云青 (Yang, J.Y.)
中科院分区:
其他
文献类型:
--
作者:
Zhang, T.;Luo, Y.;Wang;T.;杨云青 (Yang, J.Y.)

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摘要 Mllt3/Af9 是一种原癌基因,能够解除对白血病关键基因的表达调控。然而,其表达的调控仍未完全阐明。在此,我们证明 microRNA miR-297b-5p/3p 能够通过结合其 3'-非翻译区来负向调节 Mllt3/Af9 的表达。 miR-297b-5p/3p 的过表达还导致 p27Kip1 和增殖细胞核抗原的表达改变、细胞周期停滞异常、体外细胞培养物中细胞增殖、迁移和侵袭减少,并抑制裸鼠体内异种移植肿瘤的生长。这些数据表明 miR-297b-5p/3p 和 Mllt3/Af9 可能是淋巴瘤细胞增殖或癌变的关键调节因子。我们的研究结果表明,miR-297b-5p/3p 可能是诊断或治疗与 Mllt3/Af9 异常表达相关的癌症的有用分子靶点。
Abstract Mllt3/Af9 is a proto-oncogene capable of deregulating the expression of genes critical for leukemia. However, the regulation of its expression remains incompletely elucidated. Herein, we show that the microRNAs miR-297b-5p/3p are capable of regulating Mllt3/Af9 expression negatively by binding to its 3’-untranslated region. Overexpression of miR-297b-5p/3p also led to altered expression of p27Kip1 and proliferating cell nuclear antigen, abnormal cell cycle arrest, decreased cell proliferation, migration and invasion in vitro in cell cultures, and suppressed xenograft tumor growth in vivo in the nude mouse. These data demonstrate that miR-297b-5p/3p and Mllt3/Af9 might be critical regulators of lymphoma cell proliferation or carcinogenesis. Together our findings suggest that miR-297b-5p/3p might be useful molecular targets for diagnosis or treatment of cancers associated with abnormal expression of Mllt3/Af9.
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