PRJNA529086
The effect of SHP-2 knockdown and vemurafenib treatment on expression of cell cycle genes in thyroid cells with driver mutation BRAF V600E
BRAFV600E mutation is found in about 45% of papillary thyroid carcinomas and in approximately 50% of melanomas. Tumors carrying a BRAF V600E mutation constitutively activate the mitogen-activated protein kinase (MAPK) pathway, promoting cell proliferation and preventing apoptosis. Vemurafenib (PLX4032) was developed as a potent kinase inhibitor with specificity for the BRAF V600E mutation within cancer cells. SHP2 is a protein-tyrosine phosphatase that involved in signaling initiated by various growth factors and has an upstream role in stimulating MAPK signaling. To study the role of SHP2 in the growth of thyroid cancer bearing BRAF V600E mutation, we developed a model system based on the thyroid epithelial cell line Nthy-ori 3-1 that was transduced by lentiviral vector containing BRAF gene with V600E mutation. To evaluate the simultaneous effect of SHP2 knockdown and vemurafenib treatment on the oncogenic process we performed comparative transcriptome analysis of derivatives obtained by transduction of Nthy-ori 3-1 cells with “empty” viral vector and the vector harboring BRAF V600E mutation. The obtained data were compared to the data of transcriptome analysis of thyroid tumors treated by vemurafenib and after the knockdown of SHP2 using siRNA. It was shown that the knockdown of SHP2 gene in Nthy-ori 3-1with BRAF V600E mutation leads to change of expression of genes which are responsible for cell cycle (cyclin A and D) and for oncogene-induced senescence (CDKN2B, CDKN1A).