Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 190, Issue 2, Pages 469-483Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2019.10.010
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Funding
- National Natural Science Foundation of China [81672433, 81970551, 81370537, 81970726, 81472232]
- Fundamental Research Funds for the Central Universities
- Henan Provincial Natural Science Foundation [182300410323, 182300410316]
- Program for Science and Technology Innovation Talents in Universities of Henan Province (HASTIT) [13HASTIT024]
- Plan for Scientific Innovation Talent of Henan Province
- research projects on biomedical transformation of China-Japan Friendship Hospital [PYBZ1803]
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Liver cancer is the third leading cause of cancer-related death worldwide. Herein, we show that miR-149* serves as a novel tumor suppressor for liver tumorigenesis. Mice with genetic deletion of miR-149* (miR-149*(-/-) mice), which caused loss of both miR-149 and miR-149*, were considerably more susceptible to acute liver injury and hepatic carcinogenesis induced by diethylnitrosamine than wild-type mice, accompanied by increased compensatory proliferation and up-regulated gene expression of certain inflammatory cytokines. miR-149* mimics dramatically impaired liver cancer cell proliferation and migration in vitro and blocked liver cancer progression in a xenograft model. Furthermore, miR-149* strongly suppressed NF-kappa B signaling and repressed tumor necrosis factor receptor type 1 associated death domain protein expression in the NF-kappa B signaling pathway. These results reveal that miR-149*, as a novel liver tumor suppressor, may serve as a potential therapeutic target for liver cancer treatment.
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