Tumor Biology

, Volume 37, Issue 5, pp 6749–6759 | Cite as

Breast cancer cell line MDA-MB-231 miRNA profile expression after BIK interference: BIK involvement in autophagy

  • Ruth Ruiz Esparza-Garrido
  • María Eugenia Torres-Márquez
  • Rubí Viedma-Rodríguez
  • Ana Claudia Velázquez-Wong
  • Fabio Salamanca-Gómez
  • Haydeé Rosas-Vargas
  • Miguel Ángel Velázquez-Flores
Original Article

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.

Keywords

BIK MDA-MB-231 MicroRNAs Autophagy Interactome 

Notes

Acknowledgments

This article is in memory of Dr. Diego Julio Arenas Aranda†. We thank his academic support and advice during this study. We are indebted to John L. Mitchell and Veronica Vratny for English edition of this manuscript. The authors would like to thank Dr. Paola Mayocotte for LC3-II antibody supply.

This work was partially supported by a grant from PAPIIT/UNAM (IN222014).

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ruth Ruiz Esparza-Garrido
    • 1
    • 2
  • María Eugenia Torres-Márquez
    • 3
  • Rubí Viedma-Rodríguez
    • 4
  • Ana Claudia Velázquez-Wong
    • 2
  • Fabio Salamanca-Gómez
    • 5
  • Haydeé Rosas-Vargas
    • 2
  • Miguel Ángel Velázquez-Flores
    • 2
  1. 1.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)MéxicoMéxico
  2. 2.Functional Genomics Laboratory, Unit of Human Genetics Research, Children’s Hospital, National Medical Center Century XXI, Mexican Institute of Social Security (IMSS)MéxicoMéxico
  3. 3.Biochemistry DepartmentSchool of Medicine, UNAMMéxicoMéxico
  4. 4.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)TlalnepantlaMéxico
  5. 5.Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMéxicoMéxico

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