Oncotarget

Research Papers:

Gene master regulators of papillary and anaplastic thyroid cancers

Dumitru A. Iacobas _, Neha Y. Tuli, Sanda Iacobas, John K. Rasamny, Augustine Moscatello, Jan Geliebter and Raj K. Tiwari

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Oncotarget. 2018; 9:2410-2424. https://doi.org/10.18632/oncotarget.23417

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Abstract

Dumitru A. Iacobas1,4, Neha Y. Tuli2, Sanda Iacobas1, John K. Rasamny2,3, Augustine Moscatello2,3, Jan Geliebter2 and Raj K. Tiwari2

1Department of Pathology, New York Medical College, Valhalla, NY, USA

2Department of Microbiology & Immunology, New York Medical College, Valhalla, NY, USA

3Department of Otolaryngology, New York Medical College, Valhalla, NY, USA

4Center for Computational Systems Biology at Prairie View A&M University, Prairie View, TX, USA

Correspondence to:

Dumitru A. Iacobas, email: daiacobas@pvamu.edu

Keywords: 8505C anaplastic thyroid cancer cell line; BCPAP papillary thyroid cancer cell line; DDX19B; NEMP1; PANK2

Received: October 30, 2017    Accepted: December 09, 2017    Published: December 19, 2017

ABSTRACT

We hypothesize that distinct cell phenotypes are governed by different sets of gene master regulators (GMRs) whose strongly protected (by the homeostatic mechanisms) abundance modulates most cell processes by coordinating the expression of numerous genes from the corresponding functional pathways. Gene Commanding Height (GCH), a composite measure of gene expression control and coordination, is introduced to establish the gene hierarchy in each phenotype. If the hypothesis is true, than one can selectively destroy cancer nodules from a heterogeneous tissue by altering the expression of genes whose GCHs are high in cancer but low in normal cell phenotype. Here, we test the hypothesis and show its utility for the thyroid cancer (TC) gene therapy. First, we prove that malignant and cancer free surrounding areas of a surgically removed papillary TC (PTC) tumor are governed by different GMRs. Second, we show that stable transfection of a gene induces larger transcriptomic alterations in the cells where it has higher GCH than in other cells. For this, we profiled the transcriptomes of the papillary BCPAP and anaplastic 8505C TC cell lines before and after stable transfection with NEMP1, DDX19B, PANK2 or UBALD1. The four genes were selected to have similar expression levels but significantly different GCH scores in the two cell lines before transfection. Indeed, each of the four genes triggered larger alterations in the cells where they had larger GCH. Our results prove the feasibility of a personalized gene therapy approach that selectively targets the cancer cells from a tissue.


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