Male-Specific Long Noncoding RNA Inhibits Non-Small Cell Lung Cancer Proliferation and Metastasis Via TBX4

Gender affects cancer susceptibility. Currently, there are only a few studies on Y chromosome-linked long noncoding RNAs (lncRNAs), and the potential association between lncRNAs and cancers in males has not been fully elucidated. Here, we examined the expression of testis-specific transcript Y-linked 15 () in 37 males with non-small cell lung cancer (NSCLC), and performed circular chromosome conformation capture with next-generation sequencing to determine the genomic interaction regions of the gene. Our results showed that the expression levels of were lower in NSCLC tissues. Lower expression levels were associated with Tumor-Node-Metastasis (TNM) stage. A knockdown promoted malignant transformation of NSCLC cells. Based on the bioinformatics analysis of circular chromosome conformation capture data, we found that T-box transcription factor 4 (TBX4) may be a potential target gene of . The RNA immunoprecipitation and chromatin immunoprecipitation results showed that may interact with DNA (cytosine-5)-methyltransferase 3A (DNMT3A), and the knockdown increased the binding of DNMT3A to the TBX4 promoter. We concluded that low expression correlates with worse prognosis among patients with NSCLC. promotes TBX4 expression via DNMT3A-mediated regulation. The identification of lncRNAs encoded by male-specific genes may help to identify potential targets for NSCLC therapy.