Thyroid cancer is a common malignant tumor. Long non-coding RNA colon cancer-associated transcript 1 (lncRNA CCAT1) is highly expressed in many cancers; however, the molecular mechanism of CCAT1 in thyroid cancer remains unclear. Hence, this study aimed to investigate the effect of CCAT1 on human thyroid cancer cell line FTC-133. FTC-133 cells were transfected with CCAT1 expressing vector, CCAT1 shRNA, miR-143 mimic, and miR-143 inhibitor, respectively. After different treatments, cell viability, proliferation, migration, invasion, and apoptosis were measured. Moreover, the regulatory relationship of CCAT1 and miR-143, as well as miR-143 and VEGF were tested using dual-luciferase reporter assay. The relative expressions of CCAT1, miR-143, and VEGF were tested by qRT-PCR. The expressions of apoptosis-related factors and corresponding proteins in PI3K/AKT and MAPK pathways were analyzed using western blot analysis. The results suggested that CCAT1 was up-regulated in the FTC-133 cells. CCAT1 suppression decreased FTC-133 cell viability, proliferation, migration, invasion, and miR-143 expression, while it increased apoptosis and VEGF expression. CCAT1 might act as a competing endogenous RNA (ceRNA) for miR-143. Moreover, CCAT1 activated PI3K/AKT and MAPK signaling pathways through inhibition of miR-143. This study demonstrated that CCAT1 exhibited pro-proliferative and pro-metastasis functions on FTC-133 cells and activated PI3K/AKT and MAPK signaling pathways via down-regulation of miR-143. These findings will provide a possible target for clinical treatment of thyroid cancer.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. Studies have confirmed an association between microRNA (miRNA) and the BRAF mutation in various cellular biological processes of PTC. This study aimed to clarify the potential relationship between miR-150-5p and the BRAF mutation in PTC. Human PTC cell lines B-CPAP and TPC-1 were transfected with the miR-150-5p mimic, an inhibitor, and the corresponding controls. Then, cell proliferation, viability, and apoptosis were detected by bromodeoxyuridine, trypan blue exclusion, and flow cytometry assays. The expressions of the main factors of cell cycle, epithelial mesenchymal transition (EMT), and DNA mismatch repair were examined by Western blot analysis and a real-time quantitative polymerase chain reaction. Additionally, pc-BRAF was transfected into B-CPAP and TPC-1 cells to determine the relationship between miR-150-5p and BRAF . In addition, the methyl ethyl ketone (MEK)/extracellular signal-regulated kinase (ERK) signal pathway was examined using Western blot analysis. Overexpression of miR-150-5p promoted cell proliferation and viability, inhibited apoptosis, and upregulated cell cycle factor expressions at 50 passages of B-CPAP and TPC-1 cells after transfection. Overexpression of miR-150-5p led to an obvious decrease in E-cadherin expression, but enhanced N-cadherin, Slug and Vimentin, ZEB1, and Snail expression. Moreover, overexpression of miR-150-5p markedly suppressed POLD3, MSH2, and MSH3 expression. Furthermore, BRAF overexpression increased the expression level of miR-150-5p in TPC cells, and overexpression of telomerase reverse transcriptase further enhanced the promoting effect of BRAF on miR-150-5p expression in B-CPAP and TPC-1 cells. Finally, BRAF overexpression activated the MEK/ERK signal pathway in B-CPAP and TPC-1 cells. These data indicated that miR-150-5p promoted cell proliferation, suppressed apoptosis, and accelerated the EMT process by regulation of the BRAF mutation. Our findings will help elucidate the pathogenesis of PTC and identify biomarkers.

This study establishes that BCAR4 has pro-proliferative effects on normal thyroid cells. BCAR4 up-regulation promotes proliferation and suppresses apoptosis of NTHY-ORI 3-1 cells and human primary thyrocytes, and EGFR is highly expressed in BCAR4 over-expressing-cells. In contrast, BCAR4 up-regulation did not modulate cell viability or cell cycle progression when EGFR was knocked-down. Further, the phosphorylated forms of PI3K, AKT, mTOR and p70S6K were up-regulated by BCAR4 up-regulation, and the alteration in these kinases induced by BCAR4 up-regulation was abolished when EGFR was knocked-down. This study therefore revealed the pro-proliferative role of lncRNA BCAR4 in NTHY-ORI 3-1 cells and human primary thyrocytes; where BCAR4 accelerated thyroid cells proliferation by EGFR up-regulation and the modulation of PI3K/AKT/mTOR signaling. These findings indicate that targeting BCAR4 has potential in hyperthyroidism treatment.