Dataset Information

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

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.

SUBMITTER: Lai IL

PROVIDER: S-EPMC6678590 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Male-Specific Long Noncoding RNA <i>TTTY15</i> Inhibits Non-Small Cell Lung Cancer Proliferation and Metastasis via TBX4.

Lai I-Lu IL Chang Ya-Sian YS Chan Wen-Ling WL Lee Ya-Ting YT Yen Ju-Chen JC Yang Chin-An CA Hung Shih-Ya SY Chang Jan-Gowth JG

International journal of molecular sciences 20190715 14

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 (<i>TTTY15</i>) 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 re ...[more]

PMID: 31311130

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Project description:BACKGROUND:Emerging evidences have indicated that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of cancers. Dysregulation of lncRNA MIR31HG has recently been reported in several types of cancers, and researches on the function of MIR31HG in cancers suggested that MIR31HG could act as either oncogene or tumor suppressor. But the functional involvement of MIR31HG has not been studied in hepatocellular carcinoma (HCC). METHODS:In this study, MTS assays, colony formation assay, Wound-healing assay, Transwell assy, and tumor xenografts experiments were used to identify biological effects of MIR31HG on HCC cells HCC proliferation and metastasis in vitro and in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to show the interactions of MIR31HG and miR-575. The bioinformatics methods were completed to find the target genes of miR-575. And Dual-luciferase reporter assay and Western blot analysis were further used to confirm the target gene of miR-575. RESULTS:We found that overexpression of MIR31HG obviously suppressed HCC proliferation and metastasis in vitro and in vivo, whereas knockdown of MIR31HG had the opposite effects. Besides, overexpression of MIR31HG significantly decreased the expression of microRNA-575 (miR-575), which plays an oncogenic role in HCC. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay revealed that MIR31HG exerted tumor-suppressive functions by binding directly to miR-575, and there was a reciprocal inhibition between MIR31HG and miR-575 in the same RNA-induced silencing complex (RISC). Furthermore, overexpression of MIR31HG enhanced the expression of suppression of tumorigenicity 7 like (ST7L), which was identified as a downstream target gene of miR-575. Thus, MIR31HG positively regulated ST7L expression through sponging miR-575, and acted as tumor suppressor in HCC. CONCLUSIONS:Overall, our study illuminates the role of MIR31HG as a miRNA sponge in HCC, and sheds new light on lncRNA-directed diagnostics and therapeutics in HCC.

Dataset Information

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

Publications

Male-Specific Long Noncoding RNA <i>TTTY15</i> Inhibits Non-Small Cell Lung Cancer Proliferation and Metastasis via TBX4.

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