title: microRNA-18b is upregulated in breast cancer and modulates genes involved in cell migration.
abstract: 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.
authors: Oncogenomics and Cancer Proteomics Laboratory, Genomics Sciences Program, Autonomous University of Mexico City, Mexico City, Mexico.
authors: Miguel A
authors: MA
authors: Fonseca-Sanchéz
authors: Carlos
authors: C
authors: Pérez-Plasencia
authors: Jorge
authors: J
authors: Fernández-Retana
authors: Elena
authors: E
authors: Arechaga-Ocampo
authors: Laurence A
authors: LA
authors: Marchat
authors: Sergio
authors: S
authors: Rodríguez-Cuevas
authors: Veronica
authors: V
authors: Bautista-Piña
authors: Zaira E
authors: ZE
authors: Arellano-Anaya
authors: Ali
authors: A
authors: Flores-Pérez
authors: José
authors: J
authors: Diaz-Chávez
authors: César
authors: C
authors: López-Camarillo
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C522576:MIRN18A microRNA, human; D035683:MicroRNAs