Authors’ contributions ML, MJH, AK, WAS and GN conceived and designed the study. ML and MJH carried out the performed experiments. ML, WAS and GN carried out data analysis and prepared the initial manuscript. SMU provided crucial reagents. MJH, AK, SMU, WAS and GN contributed to the manuscript. WAS and GN supervised the project. All authors read and approved the final manuscript.”
“Introduction MicroRNAs

(miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally by pairing to 3’ untranslated regions (UTRs), coding sequences or 5’ UTRs of target messenger RNAs (mRNAs), which in most cases leads to translation inhibition or mRNA degradation [1]. In mammals, miRNAs are predicted to regulate the activity of approximately SB202190 chemical structure 50% of all protein-coding genes [2]. Due to the widespread regulating functions, miRNAs are involved in almost every cellular process including differentiation, cell proliferation, cell death, and tumorigenesis [3]. Hypoxia is a common feature of the tumor microenvironment [4] and has been an extensively investigated field in cancer researches demonstrating its critical role in various physiologic

and pathologic processes including cell proliferation, cell survival, angiogenesis, metabolism, tumor invasion and metastasis [5]. It is widely accepted that hypoxia represents an independent AZD3965 clinical trial adverse prognostic factor in many tumor types [4, 6]. Since the first article PLX-4720 solubility dmso demonstrated the functional link between hypoxia and miRNAs expression, which identified a specific hypoxia-regulated miRNAs (HRMs) playing an important role in cell survival in low oxygen environment [7], that more and more HRMs were identified Ribose-5-phosphate isomerase [8–12]. Although discrepancies exist among HRMs identified by different research groups, the up-regulation of miR-210 induced

by hypoxia has been consistent in all published studies in both normal and transformed cells, which implies an essential role of miR-210 for cell adaptation to hypoxia [13–15]. Not only in vitro studies correlated miR-210 with hypoxia, in vivo investigation also verified it. In tumor tissues such as breast cancer and head and neck cancers, miR-210 expression levels have been demonstrated to be correlated with hypoxia gene signatures, which suggested a direct connection between miR-210 expression and hypoxia [16, 17]. miR-210 is an intronic miRNA located within the genomic loci of transcript AK123483 [18]. While most studies reported miR-210 regulation in a hypoxia-inducible factor-1 (HIF-1)-dependent way [19–21], HIF-2-dependent [22, 23] and HIF-independent [24, 25] regulation of miR-210 have also been reported. The master HRM miR-210 has been investigated intensively, which has identified a variety of functionally important targets involved in cell cycle regulation [18, 22, 26–30], cell survival [31–36], differentiation [37–40], angiogenesis [41–51] as well as metabolism [52–57].