title: Down-regulation of TERE1/UBIAD1 activated Ras-MAPK signalling and induced cell proliferation.
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.
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Peoples Republic of China ; †Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Xia
authors.forename: Xiong
authors.initials: X
authors.lastname: Wei
authors.forename: Shimin
authors.initials: S
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Ximing
authors.initials: X
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Hong
keywords: GAPDH, human glyceraldehyde 3-phosphate dehydrogenase; IHC, immunohistochemistry; MAPK; MAPK, mitogen-activated protein kinase; MC, mock control; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NC, negative group; SCCD, Schnyder crystalline corneal dystrophy; SREBP, sterol response element binding protein; TCC, transitional cell carcinoma; TERE1/UBIAD1; cell proliferation; hTERT; siRNA, small interfering RNA