Journal
EXPERIMENTAL CELL RESEARCH
Volume 318, Issue 8, Pages 944-954Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2012.02.010
Keywords
miR-210; AIFM3; Hypoxia; Radiosensitivity; Hepatoma
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Funding
- National Natural Science Foundation of China [81071958, 30600160]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Jiangsu Province's Key Medical Department
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Hypoxia is a common feature of solid tumors and an important contributor to tumor radioresistance. miR-210 is the most consistently and robustly induced microRNA under hypoxia in different types of tumor cells and normal cells. In the present study, to explore the feasibility of miR-210 as an effective therapeutic target, lentiviral-mediated anti-sense miR-210 gene transfer technique was employed to downregulate miR-210 expression in hypoxic human hepatoma SMMC-7721, HepG2 and HuH7 cells, and phenotypic changes of which were analyzed. Hypoxia led to an increased hypoxia inducible factor-1 alpha (HIF-1 alpha) and miR-210 expression and cell arrest in the G(0)/G(1) phase in all cell lines. miR-210 downregulation significantly suppressed cell viability, induced cell arrest in the G(0)/G(1) phase, increased apoptotic rate and enhanced radiosensitivity in hypoxic human hepatoma cells. Moreover, apoptosis-inducing factor, mitochondrion-associated, 3 (AIFM3) was identified as a direct target gene of miR-210. AIFM3 downregulation by siRNA attenuated radiation induced apoptosis in miR-210 downregulated hypoxic human hepatoma cells. Taken together, these data suggest that miR-210 might be a potential therapeutic target and specific inhibition of miR-210 expression in combination with radiotherapy might be expected to exert strong anti-tumor effect on hypoxic human hepatoma cells. (C) 2012 Elsevier Inc. All rights reserved.
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