Cao Jian, Liu Lvjun, Xue Lei, Luo Yanwei, Liu Zhizhong, Guo Jie
Department of Urology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Center of Reproductive Medicine, Changsha Hospital for Maternal and Child Health Care of Hunan Normal University, Changsha, Hunan, China.
Heliyon. 2023 May 6;9(5):e16082. doi: 10.1016/j.heliyon.2023.e16082. eCollection 2023 May.
Testicular germ cell tumors (TGCTs) commonly occur in males between the ages of 15 and 34, accounting for 98% of testicular malignancies. Long non-coding RNAs (LncRNAs) have been reported to play important roles in TGCT proliferation, invasion, and functioned as prognostic biomarkers. Testis-specific transcript, Y-linked 14 (TTTY14), a long non-coding RNA localized on Chr Y q11.222, has been found to be a potential prognostic biomarker for laryngeal squamous cell carcinoma, gastric cancer, and osteosarcoma. The biological role of TTTY14 in TGCT is not well understood. In this study, we aim to clarify the biological role of TTTY14 in TGCT, as well as its role in TGCT survival prognosis and immunotherapy efficacy prediction through the deep mining of public data combined with the verification of cell biological experiments. We found that high TTTY14 expression was a poor survival prognostic factor in TGCT patients and the expression of TTTY14 might be regulated by copy number variation and DNA methylation. TTTY14 knockdown significantly inhibited the proliferation of TGCT in vitro. TTTY14 expression was positively correlated with immune cell dysfunction, and significantly negatively correlated with B cells, CD8 T cells, and macrophages, suggesting that TTTY14 may also affect the drug sensitivity by regulating the tumor immune microenvironment. In conclusion, we revealed that lncRNA TTTY14 was a novel oncogene and a biomarker in TGCT. TTTY14 may influence the drugs sensitivity through regulating the tumor immune microenvironment.
睾丸生殖细胞肿瘤（TGCT）常见于15至34岁的男性，占睾丸恶性肿瘤的98%。据报道，长链非编码RNA（LncRNA）在TGCT的增殖、侵袭中起重要作用，并可作为预后生物标志物。睾丸特异性转录本Y连锁14（TTTY14）是一种位于染色体Y q11.222上的长链非编码RNA，已被发现是喉鳞状细胞癌、胃癌和骨肉瘤的潜在预后生物标志物。TTTY14在TGCT中的生物学作用尚不清楚。在本研究中，我们旨在通过深入挖掘公共数据并结合细胞生物学实验验证，阐明TTTY14在TGCT中的生物学作用及其在TGCT生存预后和免疫治疗疗效预测中的作用。我们发现，TTTY14高表达是TGCT患者生存预后不良的因素，且TTTY14的表达可能受拷贝数变异和DNA甲基化的调控。敲低TTTY14可显著抑制TGCT在体外的增殖。TTTY14的表达与免疫细胞功能障碍呈正相关，与B细胞、CD8 T细胞和巨噬细胞呈显著负相关，提示TTTY14也可能通过调节肿瘤免疫微环境影响药物敏感性。总之，我们揭示了长链非编码RNA TTTY14是TGCT中的一种新型癌基因和生物标志物。TTTY14可能通过调节肿瘤免疫微环境影响药物敏感性。
