Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Int J Oncol. 2011 Apr;38(4):1093-101. doi: 10.3892/ijo.2011.919. Epub 2011 Jan 21.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, primarily at the post-transcriptional level. Growing evidence suggests that miRNAs function as oncogenes or tumor suppressors in human cancers. The down-regulation of miR-145 has been reported in many types of human cancer, including prostate cancer (PC), suggesting that miR-145 functions as a tumor suppressor. Using the PC cell lines, PC3 and DU145, gain-of-function assays revealed that miR-145 transfection inhibited cell proliferation, migration and invasion. Fascin homolog 1 (FSCN1), an actin-bundling protein, is a candidate target gene of miR-145 based on genome-wide gene expression analysis. A luciferase reporter assay showed a significantly decreased signal at two miR-145 target sites at the 3'UTR of FSCN1, suggesting that miR-145 directly regulates FSCN1. In FSCN1 loss-of-function assays, cell growth, migration and invasion were all inhibited, implying that FSCN1 is associated with the progression of PC. The identification of tumor suppressive miRNAs and their target genes could provide new insights into the potential mechanisms of prostate carcinogenesis.
微小 RNA（miRNAs）是一种小的非编码 RNA，主要在转录后水平调节基因表达。越来越多的证据表明，miRNAs 在人类癌症中作为癌基因或肿瘤抑制因子发挥作用。miR-145 的下调已在许多类型的人类癌症中报道，包括前列腺癌（PC），表明 miR-145 作为肿瘤抑制因子发挥作用。使用 PC 细胞系 PC3 和 DU145，功能获得实验表明，miR-145 转染抑制细胞增殖、迁移和侵袭。细丝蛋白 1（FSCN1），一种肌动蛋白成束蛋白，基于全基因组基因表达分析，是 miR-145 的候选靶基因。荧光素酶报告基因实验显示 FSCN1 的 3'UTR 上两个 miR-145 靶位点的信号显著降低，表明 miR-145 直接调节 FSCN1。在 FSCN1 功能丧失实验中，细胞生长、迁移和侵袭均受到抑制，表明 FSCN1 与 PC 的进展有关。肿瘤抑制 miRNAs 及其靶基因的鉴定可为前列腺癌发生的潜在机制提供新的见解。
