Journal
CANCER BIOLOGY & THERAPY
Volume 7, Issue 2, Pages 255-264Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.7.2.5297
Keywords
microRNA; hypoxia; ovarian cancer
Categories
Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [P50 CA083638, P01-CA83638] Funding Source: Medline
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cancer pathogenesis. We studied miRNA genes that are regulated by hypoxia in ovarian cancer cell lines by TaqMan miRNA assay containing 157 mature miRNAs. MiR-210 was the most prominent miRNA consistently stimulated under hypoxic conditions. We provide evidence for the involvement of the HIF signaling pathway in miR-210 regulation. Biocomputational analysis and in vitro assays demonstrated that e2f transcription factor 3 (e2f3), a key protein in cell cycle, is regulated by miR-210. E2F3 was further confirmed to be downregulated at the protein level upon induction of miR-210. Importantly, we found remarkably high frequency of miR-210 gene copy deletions in ovarian cancer patients (64%, n = 114) and that gene copy number correlates with miR-210 expression levels. Taken together, our results indicate that miR-210 plays a crucial role in tumor onset as a key regulator of the hypoxia response and provide evidence for a link between hypoxia and the regulation of cell cycle.
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