Abstract：
TERE1/UBIAD1 is involved in SCCD (Schnyder crystalline corneal dystrophy) and multiple human cancers. So far, the molecular mechanism of TERE1/UBIAD1 in tumourigenesis is unclear. Here, the expression levels of hTERT and TERE1/UBIAD1 in pathologically proven Chinese TCC (transitional cell carcinoma) samples were measured. It was found that decreased TERE1/UBIAD1 expression is closely related to both an increased hTERT expression and activation of Ras-MAPK signalling. Chemically modified TERE1 siRNA oligos were used to knock down TERE1 expression in human L02 cells. Cells transfected with TERE1 siRNA oligos underwent significant cell proliferation. When the levels of hTERT expression and ERK phosphorylation were measured, it was found that both of them increased in the above transfected cells, suggesting the activation of Ras-MAPK signalling. Addition of the MEK inhibitor U0126 into the transfected L02 cells described above inhibited ERK phosphorylation and hTERT expression. Our result is the initial demonstration that down-regulation of TERE1 activates Ras-MAPK signalling and induces subsequent cell proliferation. TERE1 might be a new negative regulator of Ras-MAPK signalling, which plays a pivotal role in the cell proliferation of multiple human cancers.
摘要：
TERE1/UBIAD1与SCCD（Schnyder晶状体角膜营养不良）和多种人类癌症有关。到目前为止,TERE1/UBIAD1在肿瘤发生中的分子机制尚不清楚。这里,测量了经病理证实的中国TCC（移行细胞癌）样品中hTERT和TERE1/UBIAD1的表达水平。发现降低的TERE1/UBIAD1表达与增加的hTERT表达和Ras-MAPK信号传导的激活密切相关。化学修饰的TERE1siRNA寡核苷酸用于敲低人L02细胞中的TERE1表达。用TERE1siRNA寡核苷酸转染的细胞经历了显著的细胞增殖。当测量hTERT表达和ERK磷酸化水平时，发现它们在上述转染细胞中都增加，提示Ras-MAPK信号的激活。将MEK抑制剂U0126添加到上述转染的L02细胞中抑制ERK磷酸化和hTERT表达。我们的结果是初步证明TERE1的下调激活Ras-MAPK信号并诱导随后的细胞增殖。TERE1可能是Ras-MAPK信号的一个新的负调节因子,在多种人类癌症的细胞增殖中起着关键作用。
