Long non-coding RNAs (lncRNAs) have been implicated in numerous physiological processes and diseases most notably cancers. to coordinates the transcriptional activities of these transcription factors to upregulate the RTA-408 gene encoding the gelatinase MMP9 and increase melanoma invasion. binds to and functions with AR implicating a hormone-responsive transcription factor in melanoma invasion. Thus our results may reconcile the long-established gender bias in melanoma in which males have a higher frequency RTA-408 of metastases compared to females. RESULTS expression is associated with melanoma survival outcome To identify melanoma-associated lncRNAs we performed RNA-Sequencing (RNA-seq) on three melanoma short-term cultures (MSTCs) and fibroblast short-term cultures (FSTCs) derived from the tumor microenvironment (unpublished data from Charles Yoon Brigham RTA-408 and Woman’s Hospital Boston MA). MSTCs have undergone relatively few passages outside of the patient and closely reflect the genetics of patient melanomas and provide a tractable system to study disease-relevant transcriptional changes. Of the 137 lncRNAs expressed in human melanomas (FPKM > 1 Table S1) the third most abundant lncRNA (XLOC_012568; linc00673 Refseq “type”:”entrez-nucleotide” attrs :”text”:”NR_036488.1″ term_id :”302318969″ term_text :”NR_036488.1″NR_036488.1; average FPKM = 55.33) is expressed in MSTCs but not FSTCs. Moreover this lncRNA is located within a chromosomal region commonly amplified in melanoma lung and ovarian cancers (www.broadinstitute.com/tumorscape Table S2). We confirmed increased expression of XLOC_012568 in eight MSTCs compared to three normal melanocyte controls by RT-qPCR (Tables S1 and S3 Figure 1A). In addition to melanomas the MiTranscriptome database (mitranscriptome.org) reveals that XLOC_012568 is increased in lung adenocarcinoma and squamous cell carcinomas compared to corresponding normal tissues while it is decreased in stomach cancers compared to normal tissues (Iyer et al. 2015 (Figure S1A). XLOC_012568 is also expressed in cervical ovarian and pancreatic cancers low-grade glioma and glioblastoma multiforme. Collectively these data suggest a broader role for this lncRNA in human tumorigenesis. Figure 1 is expressed in melanomas and is associated with worse overall survival There are three XLOC_012568 isoforms expressed in melanomas (Figure S1B). The most prevalent isoform locus expresses both protein-coding and functional non-coding transcripts none of the 3 isoforms exhibit protein-coding RTA-408 potential (coding potential scores expression to clinically-relevant parameters we assessed expression across 150 randomly-selected human melanomas from TCGA. Mouse monoclonal to CD53.COC53 monoclonal reacts CD53, a 32-42 kDa molecule, which is expressed on thymocytes, T cells, B cells, NK cells, monocytes and granulocytes, but is not present on red blood cells, platelets and non-hematopoietic cells. CD53 cross-linking promotes activation of human B cells and rat macrophages, as well as signal transduction. It is important to note that this analysis does not distinguish between isoforms. In agreement with results from patient-derived melanomas is expressed in 146 out of 150 randomly selected human melanomas (RPKM > 1 Table S1). Tumor depth as described by Breslow’s thickness (T measured in millimeters) is one of the most important prognostic factors in melanoma treatment. Specifically while thin tumors (≤1 mm thick) are typically treatable by surgical excision thicker tumors (>1 mm thick) have a greater possibility of reaching blood vessels and are thus more likely to metastasize requiring more aggressive treatment. expression is significantly higher in tumors at least 1 mm thick correlating with severity of the melanoma (AJCC staging classification TX/Tis/T0/T1 versus T2/T3/T4; Figure 1C). To investigate whether expression is related to disease outcome in TCGA melanomas we performed a Kaplan-Meier survival analysis comparing melanoma patients expressing high (n = 72 red line) or low (n = 70 blue line) levels of defined by the median expression (Figure 1D). High expression of is associated with shorter overall survival in melanoma RTA-408 patients (p-value = 0.0426). The median survival for the low group was 14.3 years while the high group had a median survival of only 5.3 years. Additionally the pooled hazard ratio shows an 84% increase in the risk of death for the high group (logrank HR = 1.84 95 confidence RTA-408 interval 1.03 to 3.60). Together.