Recently, messenger RNAs in eukaryotes have shown to associate with antisense (AS) transcript partners that are often referred to as long noncoding RNAs (lncRNAs) whose function is largely unknown. Here, we have identified a natural AS transcript for tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-1 (tie-1), tie-1AS lncRNA in zebrafish, mouse, and humans. In embryonic zebrafish, tie-1AS lncRNA transcript is expressed temporally and spatially in vivo with its native target, the tie-1 coding transcript and in additional locations (ear and brain). The tie-1AS lncRNA selectively binds tie-1 mRNA in vivo and regulates tie-1 transcript levels, resulting in specific defects in endothelial cell con- IntroductionOver the past few years, intensive unbiased analysis of transcriptome species has revealed that eukaryotic genomes contain a variety of RNA species. RNA molecules are essentially classified into 2 types, protein coding and nonprotein coding. The protein-coding transcripts or messenger RNA (mRNA) account for only approximately 2.3% of the human genome. 1 The majority of transcription appears to be nonprotein coding or noncoding, and the function of these noncoding transcripts is largely unknown. 2 Of the noncoding RNAs, the regulatory short noncoding RNAs, such as microRNAs, are well studied. The long noncoding RNAs (lncRNAs), which compose the largest portion of the mammalian noncoding transcriptome, are the least understood, especially its function. 3,4 lncRNAs are oriented in sense or antisense (AS) direction with respect to a protein coding locus, and located in intronic or intergenic regions. 5 In humans and mice, 61% to 72% of all transcribed regions possess lncRNAs in AS orientation, 2,6 and AS lncRNA transcripts play important roles in pathogenesis. For instance, the BACE1-AS transcript was elevated in subjects with Alzheimer disease and in amyloid precursor protein transgenic mice. 7 A growing body of evidence suggests that lncRNAs for most critical physiologic processes will be identified. Angiogenesis, the development of new vasculature from existing vasculature, is one of the fundamental developmental physiologic processes regulated in a developing vertebrate embryo. 8 Here, we identify a natural AS transcript for tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-1 (tie-1), tie-1AS lncRNA in zebrafish, mouse, and humans. tie-1 is a cell-surface tyrosine kinase receptor for angiopoietin ligands that is known to play a role in vascular development in vertebrates. [9][10][11][12] In embryonic zebrafish, tie-1AS lncRNA transcript is expressed temporally and spatially in vivo with its native target, the tie-1 coding transcript, and in additional locations (ear and brain). Its expression is controlled by a 3-kb genomic fragment in the 3Ј region of tie-1, and the bioinformatic predicted hybrid structure between tie-1:tie-1AS was detected in vivo. Capped or uncapped tie-1AS lncRNA selectively binds tie-1 mRNA in vivo and regulates tie-1...

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NgBR is a type I receptor with a single transmembrane domain and was identified as a specific receptor for Nogo-B. Our recent findings demonstrated that NgBR binds farnesylated Ras and recruits Ras to the plasma membrane, which is a critical step required for the activation of Ras signaling in human breast cancer cells and tumorigenesis. Here, we first use immunohistochemistry and real-time PCR approaches to examine the expression patterns of Nogo-B and NgBR in both normal and breast tumor tissues. Then, we examine the relationship between NgBR expression and molecular subtypes of breast cancer, and the roles of NgBR in estrogen-dependent survivin signaling pathway. Results showed that NgBR and Nogo-B protein were detected in both normal and breast tumor tissues. However, the expression of Nogo-B and NgBR in breast tumor tissue was much stronger than in normal breast tissue. The statistical analysis demonstrated that NgBR is highly associated with ER-positive/HER2-negative breast cancer. We also found that the expression of NgBR has a strong correlation with the expression of survivin, which is a well-known apoptosis inhibitor. The correlation between NgBR and survivin gene expression was further confirmed by real-time PCR. In vitro results also demonstrated that estradiol induces the expression of survivin in ER-positive T47D breast tumor cells but not in ER-negative MDA-MB-468 breast tumor cells. NgBR knockdown with siRNA abolishes estradiol-induced survivin expression in ER-positive T47D cells but not in ER-negative MDA-MB-468 cells. In addition, estradiol increases the expression of survivin and cell growth in ER-positive MCF-7 and T47D cells whereas knockdown of NgBR with siRNA reduces estradiol-induced survivin expression and cell growth. In summary, these results indicate that NgBR is a new molecular marker for breast cancer. The data suggest that the expression of NgBR may be essential in promoting ER-positive tumor cell proliferation via survivin induction in breast cancer.