期刊
GENES
卷 11, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/genes11091030
关键词
8505C cell line; apoptosis; BCPAP cell line; BRAF; CFLAR; IL6; oxidative phosphorylation; SPINT2; thyroid hormone synthesis; weighted pathway regulation
资金
- Texas A&M University System Chancellor's Research Initiative (CRI)
Publicly available (own) transcriptomic data have been analyzed to quantify the alteration in functional pathways in thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data have been generated by profiling one case of papillary thyroid carcinoma (PTC) and genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric paradigm that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase in the expression synergism ofSPINT2with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests thatSPINT2experimental overexpression may force the PTC cells into apoptosis with a negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cell lines before and after lentiviral transfection withDDX19B.
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