SDH conceived of the study, participated in its design and cooper

SDH conceived of the study, participated in its design and cooperation. All authors read and approved the final manuscript.”
“Background Survivin is a structurally and functionally unique member of the inhibitor of apoptosis protein (IAP) family. It plays an important role not only in regulating mTOR inhibition mitosis but also in inhibiting apoptosis [1, 2]. Moreover, it is highly expressed in almost all types of human tumors and fetal tissues but barely detectable in normal adult tissues [3, 4]. High levels of survivin expression have been associated with

tumor progression and angiogenesis, resistance to radiation and drug treatments, and poor survival rates in cancer patients [5, 6]. Different approaches aimed to target survivin, including small interfering RNAs [7], dominant negative mutants [8], antisense oligonucleotides [2], ribozymes [9, 10], and triplex DNA formation [11],

have been used for cancer treatment. Selleck SRT1720 However, none of these studies focus on transcriptional Selleck Ion Channel Ligand Library inhibition of survivin as a potential approach for cancer treatment. Due to the multiple functions of survivin, it seems that transcriptional inhibition of survivin could be an important mechanism to inhibit survivin expression for cancer treatment [12, 13]. Much effort has been made to explore the mechanisms by which survivin transcription is regulated. A previous report indicates that the survivin gene promoter is TATA-less and contains GC-rich sequences. Additionally, the Sp1 transcription factor induces survivin expression in HeLa cells [14]. The core promoter of survivin contains multiple CACCC or GGGTG motifs for binding of Sp1-like proteins and Kruppel-like factors (Sp/KLF) [3]. For example, KLF5, a member of Sp/KLF family, was found to be a stimulator for survivin expression in Acute Lymphoblastic Leukemia [15]. However, there are few reports related to the transcriptional regulation of survivin

in lung cancer and the precise molecular mechanism of survivin transcriptional regulation remains unclear. Poor oxygenation (hypoxia), owing to an inadequate blood supply, is a common feature of most Fossariinae solid human tumors and is associated with increased malignancy, resistance to therapy and distant metastasis [16]. Hypoxia inducible factor-1α (HIF-1α), a member of basic helix-loop-helix-PAS protein family [17, 18], is usually increased under hypoxic conditions, and can activate transcription of many genes that are critical for cellular function under hypoxic conditions [17]. Previous studies have found that down-regulation of HIF-1α could significantly decrease the levels of survivin expression in BxPc-3 pancreatic cancer cells [19] and breast cancer cells [20]. These data indicated that HIF-1α regulates expression of survivin. However, there are very few studies on mechanisms of survivin expression regulated by HIF-1α.

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