title: Breast cancer cell line MDA-MB-231 miRNA profile expression after BIK interference: BIK involvement in autophagy.
abstract: B-cell lymphoma 2 (BCL2)-interacting killer (apoptosis inducing) (BIK) has been proposed as a tumor suppressor in diverse types of cancers. However, BIK's overexpression in breast cancer (BC) and in non-small lung cancer cells (NSCLCs), associated with a poor prognosis, suggests its participation in tumor progression. In this study, we evaluated the global expression pattern of microRNAs (miRNAs), messenger RNA (mRNA) expression changes in autophagy, and autophagic flux after BIK interference. BIK gene expression was silenced by small interfering RNA (siRNA) in BC cell MDA-MB-231, and BIK interference efficiency was tested by real-time PCR and by Western blotting. BIK expression levels decreased by 75 ± 18 % in the presence of 600 nM siRNA, resulting in the abolishment of BIK expression by 94 ± 30 %. BIK interference resulted in the overexpression of 17 miRNAs that, according to the DIANA-miRPath v3.0 database, are mainly implied in the control of cell signaling, gene expression, and autophagy. The autophagy array revealed downregulation of transcripts which participate in autophagy, and their interactome revealed a complex network, where hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), α-synuclein (SNCA), unc-51-like autophagy activating kinase 1/2 (ULK1/2), and mitogen-activated protein kinase 3 (MAPK3) were shown to be signaling hubs. LC3-II expression-an autophagy marker-was increased by 169 ± 25 % after BIK interference, which indicates the involvement of BIK in autophagy. Altogether, our results indicate-for the first time-that BIK controls the expression of miRNAs, as well as the autophagic flux in MDA-MB-231 cells.
authors.affiliation: CONACyT Research Fellow, Functional Genomics Laboratory, Unit of Human Genetics Research, Children's Hospital, National Medical Center Century XXI, Mexican Institute of Social Security (IMSS), México, C.P. 06720, DF, México. uimgeneticahumana@gmail.com.|Functional Genomics Laboratory, Unit of Human Genetics Research, Children's Hospital, National Medical Center Century XXI, Mexican Institute of Social Security (IMSS), México, C.P. 06720, DF, México. uimgeneticahumana@gmail.com.
authors.forename: Ruth
authors.initials: R
authors.lastname: Ruiz Esparza-Garrido
authors.affiliation: Biochemistry Department, School of Medicine, UNAM, México, 04510, DF, México.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Torres-Márquez
authors.affiliation: Laboratorio de Biología del Desarrollo, Unidad de Morfología y Función Celular, Facultad de Estudios Superiores Iztacala (FES Iztacala), Universidad Nacional Autónoma de México (UNAM-México), 54090, Tlalnepantla, Estado de México, México.
authors.forename: Rubí
authors.initials: R
authors.lastname: Viedma-Rodríguez
authors.affiliation: Functional Genomics Laboratory, Unit of Human Genetics Research, Children's Hospital, National Medical Center Century XXI, Mexican Institute of Social Security (IMSS), México, C.P. 06720, DF, México.
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Velázquez-Wong
authors.affiliation: Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México, DF, México.
authors.forename: Fabio
authors.initials: F
authors.lastname: Salamanca-Gómez
authors.affiliation: Functional Genomics Laboratory, Unit of Human Genetics Research, Children's Hospital, National Medical Center Century XXI, Mexican Institute of Social Security (IMSS), México, C.P. 06720, DF, México.
authors.forename: Haydeé
authors.initials: H
authors.lastname: Rosas-Vargas
authors.affiliation: Functional Genomics Laboratory, Unit of Human Genetics Research, Children's Hospital, National Medical Center Century XXI, Mexican Institute of Social Security (IMSS), México, C.P. 06720, DF, México.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Velázquez-Flores
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001343:Autophagy / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D024101:Mitochondrial Proteins; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome
chemical_list: D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D012333:RNA, Messenger
keywords: Autophagy; BIK; Interactome; MDA-MB-231; MicroRNAs