Guan Xiaolei, Wang Ping, Chi Jingwei, Zhao Shihua, Wang Fei
Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao 266555, China.
Qingdao Key Lab of Thyroid Disease, Affiliated Hospital of Qingdao University, Qingdao 266555, China.
Biochem Biophys Res Commun. 2017 May 13;486(4):898-903. doi: 10.1016/j.bbrc.2017.03.117. Epub 2017 Mar 22.
A poor papillary thyroid cancer (PTC) prognosis is strongly associated with the BRAF V600E mutation. During tumor progression, levels of the high mobility group box 1 (HMGB1) protein are often dysregulated. Results herein demonstrate that HMGB1 protein levels differ between tumor and adjacent non-tumor tissue and that HMGB1 mRNA levels were higher in wild-type BRAF PTC tissues than in BRAF V600E PTC tissues (2-△Ct 0.31 ± 0.25 vs. 0.16 ± 0.12; P < 0.05). HMGB1 protein levels also differed in the same manner (wild-type BRAF PTC tissues 0.11 ± 0.04 vs. BRAF V600E PTC tissues 0.03 ± 0.03; P < 0.001). Although not detected in peripheral blood, low levels of HMGB1 were significantly related to PTC cell lymph node metastasis and extra-glandular infiltration (P = 0.045 and P = 0.002). Experimental results at the cellular level were consistent with tissues and further verified the relationship of BRAF V600E and HMGB1. These findings demonstrate that the BRAF V600E mutation down-regulates levels of HMGB1, likely through activation of the mitogen-activated protein kinase (MAPK) signaling pathways.
甲状腺乳头状癌（PTC）预后不良与BRAF V600E突变密切相关。在肿瘤进展过程中，高迁移率族蛋白B1（HMGB1）的水平常常失调。本文结果表明，肿瘤组织与相邻非肿瘤组织中的HMGB1蛋白水平存在差异，且野生型BRAF的PTC组织中的HMGB1 mRNA水平高于BRAF V600E的PTC组织（2-△Ct 0.31±0.25 vs. 0.16±0.12；P<0.05）。HMGB1蛋白水平也以同样的方式存在差异（野生型BRAF的PTC组织0.11±0.04 vs. BRAF V600E的PTC组织0.03±0.03；P<0.001）。尽管在外周血中未检测到，但低水平的HMGB1与PTC细胞的淋巴结转移和腺外浸润显著相关（P=0.045和P=0.002）。细胞水平的实验结果与组织水平一致，进一步证实了BRAF V600E与HMGB1之间的关系。这些发现表明，BRAF V600E突变可能通过激活丝裂原活化蛋白激酶（MAPK）信号通路下调HMGB1的水平。
