Downregulation of microRNAs-143 and-145 in B-cell malignancies
Downregulation of microRNAs-143 and-145 in B-cell malignancies
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DOI：
10.1111/j.1349-7006.2007.00618.x
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发表时间：
2007-12-01
期刊：
影响因子：
5.7
通讯作者：
Naoe, Tomoki
中科院分区：
文献类型：
--
作者：
Akao, Yukihiro;Nakagawa, Yoshihito;Naoe, Tomoki
近年来，研究发现microRNAs（miRNAs）的不适当表达与肿瘤的发生密切相关。在这项研究中，我们证明了miRNA（miR）-143和-145的表达，其水平先前显示在结肠癌和各种建立的癌细胞系中降低，在大多数检查的B细胞恶性肿瘤中也降低，包括慢性淋巴细胞白血病（CLL）、B细胞淋巴瘤、EB病毒（EBV）转化的B细胞系、和伯基特淋巴瘤细胞系。来自13名CLL患者的所有样本和9名B细胞淋巴瘤患者中的8名样本均显示极低的miR-143和miR-145表达。miR-143和-145的表达水平在人伯基特淋巴瘤细胞系中始终较低，并且与在EBV转化的B细胞系中观察到的细胞增殖负相关。此外，将前体或成熟miR-143和-145引入Raji细胞中导致以剂量依赖性方式发生的显著生长抑制，并且miRNA-143的靶基因被确定为ERK 5，如先前在人结肠癌DLD-1细胞中报道的。总之，这些发现表明miR-143和miR-145可用作区分B细胞恶性细胞与正常细胞的生物标志物，并通过新定义的机制促进B细胞恶性肿瘤的致癌作用。
Recently, it has been found that inappropriate expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. In this study, we demonstrated that the expression of miRNAs (miRs) -143 and -145, the levels of which were previously shown to be reduced in colon cancers and various kinds of established cancer cell lines, was also decreased in most of the B-cell malignancies examined, including chronic lymphocytic leukemias (CLL), B-cell lymphomas, Epstein-Barr virus (EBV)-transformed B-cell lines, and Burkitt lymphoma cell lines. All samples from 13 CLL patients and eight of nine B-cell lymphoma ones tested exhibited an extremely low expression of miRs-143 and -145. The expression levels of miRs-143 and -145 were consistently low in human Burkitt lymphoma cell lines and were inversely associated with the cell proliferation observed in the EBV-transformed B-cell lines. Moreover, the introduction of either precursor or mature miR-143 and -145 into Raji cells resulted in a significant growth inhibition that occurred in a dose-dependent manner and the target gene of miRNA-143 was determined to be ERK5, as previously reported in human colon cancer DLD-1 cells. Taken together, these findings suggest that miRs-143 and -145 may be useful as biomarkers that differentiate B-cell malignant cells from normal cells and contribute to carcinogenesis in B-cell malignancies by a newly defined mechanism.