title: Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro.
abstract: 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-1α (HIF-1α) 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.
authors.affiliation: Department of Radiobiology, School of Radiological Medicine and Protection, Soochow University, Suzhou, China. detachedy@yahoo.com.cn
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Ting
authors.initials: T
authors.lastname: Sun
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
authors.forename: Fenju
authors.initials: F
authors.lastname: Liu
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016373:DNA, Antisense; D015536:Down-Regulation; D018014:Gene Transfer Techniques; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000235:genetics*
chemical_list: D051033:Apoptosis Inducing Factor; D016373:DNA, Antisense; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger