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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 662 - 670 (9page)
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We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using GatewayTM technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.
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참고문헌 (30)
참고문헌 신청
Acloque, H. / 2009 / Epithelial-mesenchymal transitions : the importance of changing cell state in development and disease / J. Clin. Invest 119:1438~1449
Ahn, H. M. / 2017 / Peroxiredoxin 5 promotes the epithelial-mesenchymal transition in colon cancer / Biochem. Biophys. Res. Commun 487:580~586
Alahari, S. K. / 1993 / The fission yeast prp4+gene involved in pre-mRNA splicing codes for a predicted serine/threonine kinase and is essential for growth / Nucleic Acids Res 21:4079~4083
Arumugam, T. / 2009 / Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer / Cancer Res 69:5820~5828
Bauer, J. A. / 2010 / RNA interference(RNAi)screening approach identifies agents that enhance paclitaxel activity in breast cancer cells / Breast Cancer Res 12:R41
Ahn, H. M. / 2017 / Peroxiredoxin 5 promotes the epithelial-mesenchymal transition in colon cancer / Biochem. Biophys. Res. Commun 487:580~586
Alahari, S. K. / 1993 / The fission yeast prp4+gene involved in pre-mRNA splicing codes for a predicted serine/threonine kinase and is essential for growth / Nucleic Acids Res 21:4079~4083
Arumugam, T. / 2009 / Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer / Cancer Res 69:5820~5828
Bauer, J. A. / 2010 / RNA interference(RNAi)screening approach identifies agents that enhance paclitaxel activity in breast cancer cells / Breast Cancer Res 12:R41
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