Oncogenomics and Cancer Proteomics Laboratory, Genomics Sciences Program, Autonomous University of Mexico City, Mexico City, Mexico.
Oncol Rep. 2013 Nov;30(5):2399-410. doi: 10.3892/or.2013.2691. Epub 2013 Aug 22.
microRNAs are small non-coding RNAs of ~22 nucleotides that function at post-transcriptional level as negative regulators of gene expression. Aberrant expression of microRNAs could promote uncontrolled proliferation, migration and invasion of human cancer cells. In this study, we analyzed the expression of microRNA-18b (miR-18b) in breast cancer cell lines and in a set of clinical specimens. Our results showed that miR-18b was upregulated in four out of five breast cancer cell lines and also in breast tumors. In order to identify potential gene targets, we carried out transcriptional profiling of MDA-MB-231 breast cancer cells that ectopically expressed miR-18b. Our results showed that 263 genes were significantly modulated in miR-18b-deficient cells (fold change >1.5; P≤0.05). We found that knock-down of miR-18b induced the upregulation of 55 olfactory receptor (OR) genes and nine genes (NLRP7, KLK3, OLFM3, POSTN, MAGED4B, KIR3DL3, CRX, SEMG1 and CEACAM5) with key roles in cell migration and metastasis. Consistently, we found that ectopic inhibition of miR-18b suppressed the migration of two breast cancer cell models in vitro. In conclusion, we have uncovered genes directly or indirectly modulated by miR-18b which may represent potential therapeutic targets in breast cancer. Our data also pointed out a role of miR-18b in migration of breast cancer cells.
microRNAs 是一种约 22 个核苷酸的小非编码 RNA,在转录后水平作为基因表达的负调节剂起作用。microRNA 的异常表达可促进人类癌细胞的不受控制的增殖、迁移和侵袭。在本研究中,我们分析了 microRNA-18b(miR-18b)在乳腺癌细胞系和一组临床标本中的表达。我们的结果表明,miR-18b 在五分之四的乳腺癌细胞系中上调,并且在乳腺癌肿瘤中也上调。为了鉴定潜在的基因靶标,我们对过表达 miR-18b 的 MDA-MB-231 乳腺癌细胞进行了转录谱分析。我们的结果表明,263 个基因在 miR-18b 缺陷细胞中显著调节(倍数变化 >1.5;P≤0.05)。我们发现,敲低 miR-18b 诱导 55 个嗅觉受体(OR)基因和九个基因(NLRP7、KLK3、OLFM3、POSTN、MAGED4B、KIR3DL3、CRX、SEMG1 和 CEACAM5)的上调,这些基因在细胞迁移和转移中具有关键作用。一致地,我们发现外源性抑制 miR-18b 抑制了两种乳腺癌细胞模型在体外的迁移。总之,我们发现了受 miR-18b 直接或间接调节的基因,这些基因可能代表乳腺癌的潜在治疗靶点。我们的数据还指出了 miR-18b 在乳腺癌细胞迁移中的作用。