Wu Yu, Wang Huijuan, Zhi Jingtai, Hu Linfei, Hou Xiukun, Ruan Xianhui, Zheng Xiangqian, Liu Hui, Gao Ming
Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300600, People's Republic of China.
Department of National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300600, People's Republic of China.
Onco Targets Ther. 2019 Aug 28;12:6937-6945. doi: 10.2147/OTT.S219506. eCollection 2019.
Anaplastic thyroid carcinoma (ATC) is the most aggressive cancer in humans with no optimal treatment strategy available. The molecular mechanisms of ATC remain unclear. The aim of this study was to investigate the prognostic value and role of BRMS1 in the progression of ATC.
BRMS1 expression was examined in thyroid cell lines using Western blot analysis. Immunohistochemistry was also performed to assess BRMS1 expression in ATC and papillary thyroid cancer (PTC) tissue. Cell proliferation assays, colony formation analysis, cell migration assays, cell apoptosis analysis, and animal studies were used to examine the effects of BRMS1 expression on ATC progression.
The expression of BRMS1 was significantly lower in ATC than in PTC and was associated with poor prognosis in ATC patients. Downregulation of BRMS1 expression promoted the proliferation and migration of 8505C cells and decreased their expression of CX43. Over-expressed BRMS1 promoted the apoptosis and impaired the proliferation and migration of CAL-62 cells via upregulated CX43. In vivo, BRMS1 significantly promoted apoptosis and impaired cell proliferation.
Taken together, these findings demonstrate that decreased expression of BRMS1 is a poor prognostic biomarker in ATC patients. BRMS1 significantly promoted apoptosis and impaired cell proliferation via CX43 and P53. Loss of BRMS1 expression is therefore, one of the key pathomechanisms in ATC.
间变性甲状腺癌(ATC)是人类最具侵袭性的癌症,目前尚无最佳治疗策略。ATC的分子机制仍不清楚。本研究的目的是探讨BRMS1在ATC进展中的预后价值和作用。
采用蛋白质免疫印迹分析检测甲状腺细胞系中BRMS1的表达。还进行了免疫组织化学检测,以评估BRMS1在ATC和甲状腺乳头状癌(PTC)组织中的表达。采用细胞增殖试验、集落形成分析、细胞迁移试验、细胞凋亡分析和动物研究来检测BRMS1表达对ATC进展的影响。
BRMS1在ATC中的表达显著低于PTC,且与ATC患者的不良预后相关。BRMS1表达下调促进了8505C细胞的增殖和迁移,并降低了其CX43的表达。过表达的BRMS1通过上调CX43促进CAL-62细胞的凋亡,并损害其增殖和迁移。在体内,BRMS1显著促进凋亡并损害细胞增殖。
综上所述,这些发现表明BRMS1表达降低是ATC患者预后不良的生物标志物。BRMS1通过CX43和P53显著促进凋亡并损害细胞增殖。因此,BRMS1表达缺失是ATC的关键发病机制之一。