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hnRNP C 및 CNOT7 상호 작용을 통한 Bcl-XL mRNA 안정성 하향 조절로 인한 BTG2의 암세포 사멸 촉진
- Alternative Title
- BTG2-enhanced cancer cell death is mediated by downregulating mRNA stability of Bcl-XL via interaction with hnRNP C and CNOT7
- Author(s)
- 최용원
- Alternative Author(s)
- Yong Won Choi
- Advisor
- 임인경
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2018-02
- Language
- eng
- Alternative Abstract
- BTG2, as a founding member of anti-proliferative gene family, has been reported to render cancer cells more sensitive to chemotherapy and radiotherapy. Recent study suggested that BTG2 can activate general mRNA deadenylation and degradation as a binding partner of mRNA deadenylase, CNOT7. However, molecular mechanism of cell death regulation has not yet been fully elucidated in terms of mRNA stability regulation of BTG2. Therefore, the mechanism of enhanced cell death by BTG2 and its clinical significance were investigated. Among anti-apoptotic genes including Bcl-2, Bcl-XL, and Mcl-1, mRNA stability of Bcl-XL was reduced by BTG2. By protein chip array, HnRNP C, mRNA binding protein, was discovered as new interacting protein of BTG2. In vivo binding of BTG2 and HnRNP C was validated by immunoprecipitation. The binding of HnRNP C to 3' UTR of Bcl-XL mRNA was also confirmed by RNA immunoprecipitation and pull down assay of biotin labeled RNA. The decreased mRNA stability of Bcl-XL and enhanced cell death after cisplatin treatment by BTG2 were not observed in BTG2 mutant defective in CNOT7 binding. There results suggested that BTG2-CNOT7 complex can bind to 3' UTR of Bcl-XL mRNA by hnRNP C and decrease Bcl-XL mRNA stability with enhancing cell death. Similar to the results of cell culture experiments, response of platinum-based chemotherapy and progression-free and overall survival were better in advanced lung squamous cell carcinoma patients with high BTG2 expression. In conclusion, these results indicated that BTG2 can augment chemotherapy-induced cancer cell death by regulation of Bcl-XL mRNA stability via mediating interaction of hnRNP C-3' UTR of Bcl-XL and mRNA deadenlyase, CNOT7.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 4. Theses(Ph.D)
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