RESUMO
BACKGROUND/AIM: Several works in the past decades pointed out the key role of long intergenic non-coding RNA (lincRNA) in breast cancer development. Here in we report for first time the importance of deregulation of lincRNA RP11-400K9.4 in breast cancer cells which played a role in cell survival and migration. MATERIALS AND METHODS: After RP11-400K9.4 silencing by short hairpin RNAs or overexpression by GeneBlocks, real-time quantitative polymerase chain reaction (RT-PCR), microarray, migration, proliferation and viability assay were performed. RESULTS: RP11-400K9.4 expression was mainly in the cytoplasmic fraction in 2D culture. Overexpression of RP11-400K9.4 led to a reduction of migration by MCF-7 and MDA-MB-368 cells and an increase in cellular survival after UV-C radiation. Bioinformatic analyses highlighted irradiation-induced DNA damage, DNA repair and cell-cycle pathways as the mainly affected by RP11-400K9.4. Furthermore RT-PCR assay demonstrated the overexpression of baculoviral IAP repeat containing 3 (BIRC3) a known oncogene that promotes radiotherapy resistance through the nuclear factor kappa B (NFĸB) pathway. CONCLUSION: RP11-400K9.4 participates in the modulation of migration and survival processes probably via the BIRC3/NFĸB pathway.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Apoptose , Neoplasias da Mama/genética , Ciclo Celular , Feminino , Humanos , Células Tumorais CultivadasRESUMO
Platinum drugs continue to be major chemotherapy drugs for cancer treatment. Nevertheless, acquired or intrinsic resistance to these compounds is common in human tumors. One important mechanism for this resistance is the avoidance of cells entering the apoptotic pathway. Nuclear factor-kappa B (NF-kappa B, NF-kappaB) is a pleiotropic transcription factor key in determining the death threshold of human cells. This factor is important in the final response of cells to platinum drugs, as exemplified by in vitro and in vivo models showing that inhibition of NF-kappaB sensitizes cancer cells to the effects of these drugs. New approaches focusing on the inhibition of NF-kappaB could help to minimize or even eliminate intrinsic or acquired resistance to platinum drugs.
