TGF-beta Suppresses COX-2 Expression by Tristetraprolin-Mediated RNA Destabilization in A549 Human Lung Cancer Cells.
- Author:
Soyeong KANG
1
;
Ahrum MIN
;
Seock Ah IM
;
Sang Hyun SONG
;
Sang Gyun KIM
;
Hyun Ah KIM
;
Hee Jun KIM
;
Do Youn OH
;
Hyun Soon JONG
;
Tae You KIM
;
Yung Jue BANG
Author Information
- Publication Type:Original Article
- Keywords: Cyclooxygenase 2; Transforming growth factor beta; Tristetraprolin; RNA stability; Smad3
- MeSH: Adenocarcinoma; Blotting, Northern; Blotting, Western; Cyclooxygenase 2; Dactinomycin; Down-Regulation; Epithelial Cells; Humans; Lung; Lung Neoplasms*; RNA Interference; RNA Stability; RNA*; RNA, Messenger; Transforming Growth Factor beta*; Tristetraprolin
- From:Cancer Research and Treatment 2015;47(1):101-109
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor beta (TGF-beta) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-beta can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-beta-responsive and overexpress COX-2. MATERIALS AND METHODS: Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-beta. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference. RESULTS: We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-beta. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-beta, suggesting that TGF-beta-induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-beta rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-beta. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-beta. CONCLUSION: The results of this study show that TGF-beta down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells.
