Miguel A FernÁndez-Rojas1, Jorge Melendez-Zajgla2, Vilma Maldonado Lagunas3. 1. Epigenetics Laboratory, Instituto Nacional de Medicina Genómica, México City, México. 2. Functional Genomics Laboratory, Instituto Nacional de Medicina Genómica, México City, México. 3. Epigenetics Laboratory, Instituto Nacional de Medicina Genómica, México City, México vmaldonado@inmegen.gob.mx.
Abstract
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. Copyright
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. Copyright
Authors: Aravind Subramanian; Pablo Tamayo; Vamsi K Mootha; Sayan Mukherjee; Benjamin L Ebert; Michael A Gillette; Amanda Paulovich; Scott L Pomeroy; Todd R Golub; Eric S Lander; Jill P Mesirov Journal: Proc Natl Acad Sci U S A Date: 2005-09-30 Impact factor: 11.205
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