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Double gene siRNA knockdown of mutant p53 and TNF induces apoptosis in triple-negative breast cancer cells

Authors Pileczki V, Pop L, Braicu C, Budisan L, Bolba Morar G, del C Monroig-Bosque P, Sandulescu RV, Berindan-Neagoe I

Received 18 April 2016

Accepted for publication 17 July 2016

Published 11 November 2016 Volume 2016:9 Pages 6921—6933

DOI https://doi.org/10.2147/OTT.S110719

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 2

Editor who approved publication: Dr Faris Farassati


Valentina Pileczki,1,2 Laura Pop,1 Cornelia Braicu,1 Livia Budisan,1 Gabriela Bolba Morar,3 Paloma del C Monroig-Bosque,4 Robert V Sandulescu,2 Ioana Berindan-Neagoe1,5,6

1The Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Department of Analytical Chemistry, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 3Department of Senology, the Oncology Institute “Prof Dr Ion Chiricuta”, Cluj-Napoca, Romania; 4University of Puerto Rico School of Medicine, San Juan, Puerto Rico; 5MedFuture Research Center for Advanced Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 6Department of Functional Genomics and Experimental Pathology, the Oncology Institute “Prof Dr Ion Chiricuta”, Cluj-Napoca, Romania

Abstract: Apoptosis is the major downregulated pathway in cancer. Simultaneous inhibition using specific small interfering RNA (siRNA) of two key player genes, p53 and TNF, is an interesting and feasible strategy when it comes to investigating various molecular pathways and biological processes in triple-negative breast cancer (TNBC), which is one of the most aggressive and therapeutically unresponsive forms of breast cancers. Our present research focuses on evaluating the impact of double p53-siRNA and TNF-siRNA knockdown at a cellular level, and also evaluating cell proliferation, apoptosis, induction of autophagy, and gene expression by using reverse transcription polymerase chain reaction array approaches. Simultaneous inhibition of p53 and TNF in Hs578T TNBC human cell line revealed a panel of up- and downregulated genes involved in apoptosis. Furthermore, the effects of double gene knockdown were validated in a second TNBC cell line, MDA-MB-231, by using reverse transcription polymerase chain reaction TaqMan assay. All our findings help in understanding the functional mechanisms of extrinsic apoptosis, cell signaling pathways, and the mechanisms involved in tumor cell survival, growth, and death in TNBC.

Keywords: apoptosis, double gene silencing, mut-p53, TNF, TNBC

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