Abstract
Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that represses expression of various tumor suppressor genes. In the present study, we identified miR-137 as a potential regulator of CtBP1 expression in melanoma cells. Expression of miR-137 in melanoma cell lines was found to inversely correlate with CtBP1 levels. Target Scan predicted a putative site for miR-137 within the CtBP1 3′ untranslated region (3′UTR) at nt 710-716, which is highly conserved across species. To explore the mechanism of miR-137 targeting CtBP1, we performed an Argonaute 2 (Ago2)-pull down assay, and miR-137 was identified in complex with CtBP1 mRNA. miR-137 suppressed CtBP1 3′ UTR luciferase-reporter activity, and this effect was lost with deletion of the putative 3′ UTR target-site. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced expression levels of CtBP1. Furthermore, expression of miR-137 increased the immediate downstream effectors of CtBP1, such as E-cadherin and Bax. The human miR-137 gene is located at chromosome 1p22, which has previously been determined to be a susceptive region for melanoma. This study suggests miR-137 may act as a tumor suppressor by directly targeting CtBP1 to inhibit epithelial-mesenchymal transition (EMT) and inducing apoptosis of melanoma cells, thus illustrating a functional link between miR-137 and CtBP1 in melanoma development
| Original language | English (US) |
|---|---|
| Pages (from-to) | 133-137 |
| Number of pages | 5 |
| Journal | International Journal of Biological Sciences |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2011 |
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Keywords
- CtBP1
- Melanoma
- Transcription
- Tumor suppressor
- miR-137
Cite this
MicroRNA-137 targets carboxyl-terminal binding protein 1 in melanoma cell lines. / Deng, Yu; Deng, Hui; Bi, Feng; Liu, Jing; Bemis, Lynn T.; Norris, David; Wang, Xiao Jing; Zhang, Qinghong.
In: International Journal of Biological Sciences, Vol. 7, No. 1, 01.01.2011, p. 133-137.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA-137 targets carboxyl-terminal binding protein 1 in melanoma cell lines
AU - Deng, Yu
AU - Deng, Hui
AU - Bi, Feng
AU - Liu, Jing
AU - Bemis, Lynn T.
AU - Norris, David
AU - Wang, Xiao Jing
AU - Zhang, Qinghong
PY - 2011/1/1
Y1 - 2011/1/1
N2 - Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that represses expression of various tumor suppressor genes. In the present study, we identified miR-137 as a potential regulator of CtBP1 expression in melanoma cells. Expression of miR-137 in melanoma cell lines was found to inversely correlate with CtBP1 levels. Target Scan predicted a putative site for miR-137 within the CtBP1 3′ untranslated region (3′UTR) at nt 710-716, which is highly conserved across species. To explore the mechanism of miR-137 targeting CtBP1, we performed an Argonaute 2 (Ago2)-pull down assay, and miR-137 was identified in complex with CtBP1 mRNA. miR-137 suppressed CtBP1 3′ UTR luciferase-reporter activity, and this effect was lost with deletion of the putative 3′ UTR target-site. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced expression levels of CtBP1. Furthermore, expression of miR-137 increased the immediate downstream effectors of CtBP1, such as E-cadherin and Bax. The human miR-137 gene is located at chromosome 1p22, which has previously been determined to be a susceptive region for melanoma. This study suggests miR-137 may act as a tumor suppressor by directly targeting CtBP1 to inhibit epithelial-mesenchymal transition (EMT) and inducing apoptosis of melanoma cells, thus illustrating a functional link between miR-137 and CtBP1 in melanoma development
AB - Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that represses expression of various tumor suppressor genes. In the present study, we identified miR-137 as a potential regulator of CtBP1 expression in melanoma cells. Expression of miR-137 in melanoma cell lines was found to inversely correlate with CtBP1 levels. Target Scan predicted a putative site for miR-137 within the CtBP1 3′ untranslated region (3′UTR) at nt 710-716, which is highly conserved across species. To explore the mechanism of miR-137 targeting CtBP1, we performed an Argonaute 2 (Ago2)-pull down assay, and miR-137 was identified in complex with CtBP1 mRNA. miR-137 suppressed CtBP1 3′ UTR luciferase-reporter activity, and this effect was lost with deletion of the putative 3′ UTR target-site. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced expression levels of CtBP1. Furthermore, expression of miR-137 increased the immediate downstream effectors of CtBP1, such as E-cadherin and Bax. The human miR-137 gene is located at chromosome 1p22, which has previously been determined to be a susceptive region for melanoma. This study suggests miR-137 may act as a tumor suppressor by directly targeting CtBP1 to inhibit epithelial-mesenchymal transition (EMT) and inducing apoptosis of melanoma cells, thus illustrating a functional link between miR-137 and CtBP1 in melanoma development
KW - CtBP1
KW - Melanoma
KW - Transcription
KW - Tumor suppressor
KW - miR-137
UR - http://www.scopus.com/inward/record.url?scp=79952458197&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952458197&partnerID=8YFLogxK
U2 - 10.7150/ijbs.7.133
DO - 10.7150/ijbs.7.133
M3 - Article
C2 - 21278922
AN - SCOPUS:79952458197
VL - 7
SP - 133
EP - 137
JO - International Journal of Biological Sciences
JF - International Journal of Biological Sciences
SN - 1449-2288
IS - 1
ER -