LINC00162 Silencing Enhances Sorafenib Sensitivity and Inhibits Thyroid Cancer Cells Progression through Modulation of MAPK Signaling and Apoptosis

Many studies have reported aberrant expression of the lncRNAs and indicated their role in cancer progression and drug resistance across various cancers. In this study, we aimed to evaluate the effect of the LINC00162 lncRNA in the chemosensitivity of thyroid cancer cells, both individually and in combination with sorafenib on various biological processes. In this regard, we conducted our experiments in several groups: 1) LINC00162 siRNA transfected cells, 2) Sorafenib treated cells, 3) Cells that received siRNA transfection and sorafenib treatment combination 4) Control group. MTT assay results revealed that siRNA-mediated silencing of the LINC00162 reduced the viability of the BC-PAP thyroid cancer cells, and increased the sensitivity of the cancerous cells to sorafenib by reducing its IC50. Flow cytometry assessment of apoptosis and cell cycle progression indicated that LINC00162 silencing induced apoptosis and Sub-G1 cell cycle arrest while its combination with sorafenib significantly increased apoptosis rate and also arrested cells in the G2-M phase in addition to Sub-G1 phase. This combination treatment increased the expression of apoptosis-related genes Bax, Caspase3, and Caspase9 while decreasing Bcl-2 expression. Additionally, significant inhibition of cell-cycle related gene c-myc and upregulation of p53 were observed following combination treatment. Furthermore, the combination therapy reduced the migration of the BC-PAP cells through the downregulation of MMP-3 and MMP-9. Colony sizes and numbers also decreased following siRNA-mediated silencing of LINC00162 and sorafenib treatment. qRT-PCR analysis of stemness-involved genes, including Nanog, Sox2, Cd44, and CD133 confirmed colony formation assay’s findings. To understand the underlying mechanisms of LINC0162 lncRNA in thyroid cancer progression, we evaluated the expression of the MAPK pathway genes. Our finding indicated that LINC00162 silencing, in combination with sorafenib, reduced the expression of the MAPK, RAS, and RAF genes. From our findings, we can be conclude that LINC00162 silencing individually and combined with sorafenib reduced the progression and viability of thyroid cancer cells through modulating genes involved in key pathways and could be considered a new therapeutic approach in papillary thyroid cancer (PTC) treatment.