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Open AccessArticle

Male-Specific Long Noncoding RNA TTTY15 Inhibits Non-Small Cell Lung Cancer Proliferation and Metastasis via TBX4

1
Epigenome Research Center, China Medical University Hospital, Taichung 404, Taiwan
2
Department of Laboratory Medicine, China Medical University Hospital, Taichung 404, Taiwan
3
Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413, Taiwan
4
Division of General Pediatrics, Children’s Hospital of China Medical University, Taichung 404, Taiwan
5
College of Medicine, China Medical University, Taichung 404, Taiwan
6
Division of Laboratory Medicine, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan
7
Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3473; https://doi.org/10.3390/ijms20143473
Received: 19 June 2019 / Revised: 11 July 2019 / Accepted: 13 July 2019 / Published: 15 July 2019
(This article belongs to the Special Issue Molecular Pathology of Lung and Thoracic Cancers)
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. View Full-Text
Keywords: TTTY15; lncRNA; non-small cell lung cancer; TBX4; methylation; DNMT TTTY15; lncRNA; non-small cell lung cancer; TBX4; methylation; DNMT
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MDPI and ACS Style

Lai, I.-L.; Chang, Y.-S.; Chan, W.-L.; Lee, Y.-T.; Yen, J.-C.; Yang, C.-A.; Hung, S.-Y.; Chang, J.-G. Male-Specific Long Noncoding RNA TTTY15 Inhibits Non-Small Cell Lung Cancer Proliferation and Metastasis via TBX4. Int. J. Mol. Sci. 2019, 20, 3473.

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