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Hokkaido University Collection of Scholarly and Academic Papers >
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Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of microRNA-124
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| Title: | Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of microRNA-124 |
| Authors: | Dong, Peixin Browse this author →KAKEN DB | | Xiong, Ying Browse this author | | Watari, Hidemichi Browse this author →KAKEN DB | | Hanley, Sharon JB Browse this author →KAKEN DB | | Konno, Yosuke Browse this author | | Ihira, Kei Browse this author | | Suzuki, Fumihiko Browse this author →KAKEN DB | | Yamada, Takahiro Browse this author →KAKEN DB | | Kudo, Masataka Browse this author | | Yue, Junming Browse this author | | Sakuragi, Noriaki Browse this author →KAKEN DB |
| Issue Date: | 21-Oct-2016 |
| Publisher: | Macmillan Publishers |
| Journal Title: | Scientific Reports |
| Volume: | 6 |
| Start Page: | 35480 |
| Publisher DOI: | 10.1038/srep35480 |
| Abstract: | Derepression of wild-type p53 by suppressing its negative inhibitor iASPP (Inhibitor of apoptosis-stimulating protein of p53) represents a potential therapeutic option for cervical cancer (CC). Here, we reported a novel functional significance of iASPP upregulation in cervical tumorigenesis: iASPP acts as a key promoter of CC cell proliferation, epithelial-mesenchymal transition, invasion and cancer stemness, by interacting with p53 to suppress p53-mediated transcription of target genes and reducing p53-responsive microRNA-34a levels. Moreover, we demonstrate that miR-124, directly targeting iASPP, reduces expression of iASPP and attenuates CC cell growth and invasiveness. Low miR-124 expression is inversely correlated with increased expression of iASPP mRNA in CC tissues. In a cohort of 40 patients with CC, the low miR-124 expression was correlated with poor 5-year overall survival (P = 0.0002) and shorter disease-free survival 5-year (P = 0006). Treatment with the DNA methyltransferase inhibitor Zebularine increases miR-124 expression and retards CC cell growth and invasion with minimal toxicity to normal cells. Even at a non-toxic concentration, Zebularine was effective in suppressing CC cell invasion and migration. Altogether, the restoration of miR-124 reduces iASPP expression and leads to p53-dependent tumor suppression, suggesting a therapeutic strategy to treat iASPP-associated CC. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/63170 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 董 培新
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