let-7 microRNA functions as a potential growth suppressor in human colon cancer cells
let-7 microRNA functions as a potential growth suppressor in human colon cancer cells
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DOI：
10.1248/bpb.29.903
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发表时间：
2006-05-01
影响因子：
2
通讯作者：
Naoe, Tomoki
中科院分区：
文献类型：
--
作者：
Akao, Yukihiro;Nakagawa, Yoshihito;Naoe, Tomoki
microRNA（miRNAs）是内源性表达的RNA，长度为18-25个核苷酸，通过与靶mRNA结合来抑制蛋白质翻译。miRNA参与了许多细胞过程，包括细胞增殖、分化和死亡。最近，let-7 miRNAs被发现调节人RAS癌基因的表达，并且在人肺肿瘤中经常被下调。在这项研究中，我们检测了let-7 miRNAs在人结肠癌肿瘤和细胞系中的表达，结果6例中有2例和3例细胞系中有1例显示let-7表达降低。当let-7低表达DLD-1人结肠癌细胞用let-7a-1前体miRNA转染时，细胞经历显著的生长抑制，所述前体miRNA位于染色体9q22.3。此时，RAS和c-myc蛋白的水平在转染后降低，而它们的mRNA的水平几乎保持不变。这些发现表明let-7 miRNA参与结肠癌细胞的生长。因此，miRNA可能为新型RNA抗癌剂提供基础。
MicroRNAs (miRNAs) are endogenously expressed RNAs, 18-25 nucleotides in length, that repress protein translation through binding to target mRNAs. miRNAs have been implicated in many cellular processes including cell proliferation, differentiation, and death. Recently, let-7 miRNAs were found to regulate human RAS oncogene expression and to be often down-regulated in human lung tumors. In this study, we examined the expression of let-7 miRNAs in human colon cancer tumors and cell lines, with the result that 2 of 6 cases and 1 of 3 cell lines showed reduced expression of let-7. When let-7 low-expressing DLD-1 human colon cancer cells were transfected with let-7a-1 precursor miRNA, which is located at chromosome 9q22.3, the cells underwent significant growth suppression. At that time, the levels of RAS and c-myc proteins were lowered after the transfection, whereas the levels of both of their mRNAs remained almost unchanged. These findings suggest the involvement of let-7 miRNA in the growth of colon cancer cells. Thus, miRNAs might provide a basis for novel RNA anti-cancer agents.