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Abstract
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 (TTTY15) 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 TTTY15 gene. Our results showed that the expression levels of TTTY15 were lower in NSCLC tissues. Lower TTTY15 expression levels were associated with Tumor-Node-Metastasis (TNM) stage. A TTTY15 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 TTTY15. The RNA immunoprecipitation and chromatin immunoprecipitation results showed that TTTY15 may interact with DNA (cytosine-5)-methyltransferase 3A (DNMT3A), and the TTTY15 knockdown increased the binding of DNMT3A to the TBX4 promoter. We concluded that low TTTY15 expression correlates with worse prognosis among patients with NSCLC. TTTY15 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.
Highlights
Lung cancer is one of the most frequently diagnosed malignant tumors and remains the leading cause of cancer-related deaths worldwide [1,2]
To determine whether testis-specific transcript Y-linked 15 (TTTY15) plays a role in non-small cell lung cancer (NSCLC), we tested the expression of TTTY15 in 37 pairs of NSCLC tissue samples and their paired nontumor tissue samples
Sci. 2019, 20, 3473 tumor size (Table 1). These results indicate that TTTY15 may participate in NSCLC tumorigenesis
Summary
Lung cancer is one of the most frequently diagnosed malignant tumors and remains the leading cause of cancer-related deaths worldwide [1,2]. Since diagnosis is usually made at advanced stages of the disease, the five year overall survival rate among NSCLC patients is under 20% [5,6]. The overall survival rate is two-fold higher among women than among men. The protein-coding genes of the X and Y chromosomes have been relatively well characterized. Human Y chromosome deletions and rearrangements are associated with various cancers, including prostate cancer [7,8], bladder cancer [9], male sex cord stromal tumors, lung cancer [10,11], and esophageal carcinoma [12], indicating the presence of oncogenes and tumor suppressor genes on this chromosome. The chromosomal regions responsible for the production of noncoding RNAs are not well known
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