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Down-regulation of TERE1/UBIAD1 activated Ras-MAPK signalling and induced cell proliferation.

Xia Y, Wei X, Wu S, Wang B, Wang X, Hong L - Cell Biol Int Rep (2010) (2010)

Bottom Line: It was found that decreased TERE1/UBIAD1 expression is closely related to both an increased hTERT expression and activation of Ras-MAPK signalling.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.Our result is the initial demonstration that down-regulation of TERE1 activates Ras-MAPK signalling and induces subsequent cell proliferation.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Knocking down TERE1 expression with siRNA oligos up-regulates hTERT expression(A) mRNA expression level of TERE1 and hTERT in human L02 cells transfected with TERE1 siRNA oligos. NC, negative control (random siRNA oligos); MC, mock control (no siRNA oligos); 291, TERE1-291-siRNA oligos; 322, TERE1-322-siRNA oligos. (B) Protein level of TERE1 and hTERT in the above experiment. TERE1 expression was silenced by TERE1 siRNA oligos. The relative intensities of TERE1 bands are shown in the graph. The protein level of hTERT increased (P<0.05) in TERE1 siRNA-transfected cells. ERK phosphorylation level increased as well.
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Figure 2: Knocking down TERE1 expression with siRNA oligos up-regulates hTERT expression(A) mRNA expression level of TERE1 and hTERT in human L02 cells transfected with TERE1 siRNA oligos. NC, negative control (random siRNA oligos); MC, mock control (no siRNA oligos); 291, TERE1-291-siRNA oligos; 322, TERE1-322-siRNA oligos. (B) Protein level of TERE1 and hTERT in the above experiment. TERE1 expression was silenced by TERE1 siRNA oligos. The relative intensities of TERE1 bands are shown in the graph. The protein level of hTERT increased (P<0.05) in TERE1 siRNA-transfected cells. ERK phosphorylation level increased as well.

Mentions: Since TERE1 is widely expressed in various human cell types, human L02 cells were utilized to study the relationship between TERE1 and tumourigenesis. To test if down-regulation of TERE1 is the direct cause for tumourigenesis, chemically modified siRNA oligos were used to knock down the expression level of TERE1 in human L02 cells. TERE1-291, 322-siRNA oligos down-regulated the expression of TERE1 in both mRNA and protein levels (Figure 2). Where TERE1 expression was knocked down by siRNA oligos, hTERT expression significantly increased in both mRNA and protein levels.


Down-regulation of TERE1/UBIAD1 activated Ras-MAPK signalling and induced cell proliferation.

Xia Y, Wei X, Wu S, Wang B, Wang X, Hong L - Cell Biol Int Rep (2010) (2010)

Knocking down TERE1 expression with siRNA oligos up-regulates hTERT expression(A) mRNA expression level of TERE1 and hTERT in human L02 cells transfected with TERE1 siRNA oligos. NC, negative control (random siRNA oligos); MC, mock control (no siRNA oligos); 291, TERE1-291-siRNA oligos; 322, TERE1-322-siRNA oligos. (B) Protein level of TERE1 and hTERT in the above experiment. TERE1 expression was silenced by TERE1 siRNA oligos. The relative intensities of TERE1 bands are shown in the graph. The protein level of hTERT increased (P<0.05) in TERE1 siRNA-transfected cells. ERK phosphorylation level increased as well.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475436&req=5

Figure 2: Knocking down TERE1 expression with siRNA oligos up-regulates hTERT expression(A) mRNA expression level of TERE1 and hTERT in human L02 cells transfected with TERE1 siRNA oligos. NC, negative control (random siRNA oligos); MC, mock control (no siRNA oligos); 291, TERE1-291-siRNA oligos; 322, TERE1-322-siRNA oligos. (B) Protein level of TERE1 and hTERT in the above experiment. TERE1 expression was silenced by TERE1 siRNA oligos. The relative intensities of TERE1 bands are shown in the graph. The protein level of hTERT increased (P<0.05) in TERE1 siRNA-transfected cells. ERK phosphorylation level increased as well.
Mentions: Since TERE1 is widely expressed in various human cell types, human L02 cells were utilized to study the relationship between TERE1 and tumourigenesis. To test if down-regulation of TERE1 is the direct cause for tumourigenesis, chemically modified siRNA oligos were used to knock down the expression level of TERE1 in human L02 cells. TERE1-291, 322-siRNA oligos down-regulated the expression of TERE1 in both mRNA and protein levels (Figure 2). Where TERE1 expression was knocked down by siRNA oligos, hTERT expression significantly increased in both mRNA and protein levels.

Bottom Line: It was found that decreased TERE1/UBIAD1 expression is closely related to both an increased hTERT expression and activation of Ras-MAPK signalling.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.Our result is the initial demonstration that down-regulation of TERE1 activates Ras-MAPK signalling and induces subsequent cell proliferation.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus