Mps1 is associated with the BRAFV600E mutation but does not rely on the classic RAS/RAF/MEK/ERK signaling pathway in thyroid carcinoma

Abstract

Abstract.In previous studies, the B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation has been identified in multiple malignant tumors. BRAF V600E has been revealed to contribute to tumorigenesis by the activation of phospho-mitogen-activated protein kinases (MAPKs) and their downstream Monopolar spindle 1 (Mps1), leading to chromosome euploidy and tumor development. In the present study, the presence of phospho-MAPK and Mps1 in 161 thyroid carcinoma cases with complete clinical parameters was analyzed by immunohistochemistry, and the BRAF mutation was detected by polymerase chain reaction-direct sequencing. It was revealed that BRAF V600E was present in ~34% of thyroid cancer cases and was associated with age, clinical tumor stage and lymph node stage. However, the association of BRAF V600E with overall survival was not statistically significant. The expression of Mps1 was significantly increased in tumor tissues with BRAF V600E , however, this did not affect the expression of phospho-MAPK in thyroid carcinomas. Collectively, the results of the present study suggested that BRAF V600E may regulate the expression of Mps1 in MAP kinase independent ways in thyroid carcinoma. Therefore, Mps1 expression is associated with BRAF V600E while the upstream signaling of phospho-MAPK has no relevance. The specific mechanisms of BRAF V600E and the unknown pathway associated with Mps1 exhibit potential for further study, and provide a theoretical basis for the molecular treatment of thyroid carcinoma.

Bioinformatic Analysis of the Effect of the Sirtuin Family on Differentiated Thyroid Carcinoma

“…SIRT6 was most positively associated with LSM7 and FKBP8 but most negatively associated with STT3B and CLCN3 while genes most positively associated with SIRT7 were SPSB3 , ZGPAT , PUS1 , and TSEN54 but PRKAR2A and PDZD8 were the most negatively associated with SIRT7 (Figures 5 and 6 ). Specially, BRAF mutation is the most common gene alteration in DTC [ 30 ]. We examined the correlation between SIRTs and BRAF and found that BRAF was positively associated with SIRT1 , SIRT2 , SIRT3 , SIRT4 , SIRT5 , and 7 but negatively associated with SIRT6 ( p < 0.05).…”

miR‑27a‑3p regulates proliferation and apoptosis of colon cancer cells by potentially targeting BTG1

“…In human cancers, aberrant activation of the RAF/MEK/ERK signaling pathway is frequently observed. There has been increasing evidence revealing the importance of the RAF/MEK/ERK signaling pathway in tumorigenesis (65–67). The relatively high frequency of activating mutations of RAS (~20% of all human types of cancer), an upstream activator of the well-established RAF/MEK/ERK signaling cascade, as well as frequent activating mutations in the BRAF kinase gene (~7% of all human types of cancer) have been observed (68).…”