Department of Urology, Institute of Urology, West China Hospital of Sichuan University, No.37 Guoxue Alley, Chengdu, 610000, Sichuan, PR China; Department of Urology, The Second Peoples Hospital of Deyang City, Deyang, 618000, Sichuan, PR China.
Department of Urology, Institute of Urology, West China Hospital of Sichuan University, No.37 Guoxue Alley, Chengdu, 610000, Sichuan, PR China.
Int J Biochem Cell Biol. 2020 May;122:105702. doi: 10.1016/j.biocel.2020.105702. Epub 2020 Feb 19.
As reported in numerous studies, long non-coding RNAs (lncRNAs) exert significant effect on the regulation of tumor development. LncRNA TMPO antisense RNA 1 (TMPO-AS1) has been confirmed to be implicated in the development of several cancers. However, its clinical significance is still largely unknown in bladder cancer (BCa). In this study, high expression of TMPO-AS1 was revealed in BCa tissues and cell lines, and TMPO-AS1 predicted poor prognosis. Moreover, TMPO-AS1 facilitated cell growth. Additionally, TMPO-AS1 also boosted the migration and invasion of BCa cells. Mechanistically, overexpressed EBF transcription factor 1 (EBF1) in BCa cell was verified to promote the transcription of TMPO-AS1. Later, we found that TMPO-AS1 was a cytoplasmic RNA and could sponge miR-98-5p. Besides, it was validated that EBF1 is a target gene of miR-98-5p and negatively correlated with miR-98-5p in terms of expression level. According to the results of rescue experiments, we observed that EBF1 overexpression restored the repressive effect of TMPO-AS1 silencing on BCa development. Our research is the first to disclose the biological role and molecular mechanism of TMPO-AS1 in BCa, and TMPO-AS1 might be identified as a new therapeutic target for BCa patients.
已有大量研究表明，长链非编码 RNA（lncRNA）对肿瘤的发生发展具有重要的调控作用。lncRNA TMPO 反义 RNA1（TMPO-AS1）已被证实参与了多种癌症的发生发展。然而，其在膀胱癌（BCa）中的临床意义仍知之甚少。在本研究中，TMPO-AS1 在 BCa 组织和细胞系中呈高表达，且 TMPO-AS1 预测预后不良。此外，TMPO-AS1 促进了细胞的生长。进一步研究发现，TMPO-AS1 还促进了 BCa 细胞的迁移和侵袭。机制上，在 BCa 细胞中过表达 EBF 转录因子 1（EBF1）被证实可以促进 TMPO-AS1 的转录。随后，我们发现 TMPO-AS1 是一种细胞质 RNA，可以与 miR-98-5p 结合。此外，还验证了 EBF1 是 miR-98-5p 的靶基因，其表达水平与 miR-98-5p 呈负相关。根据挽救实验的结果，我们观察到过表达 EBF1 可以恢复 TMPO-AS1 沉默对 BCa 发生发展的抑制作用。我们的研究首次揭示了 TMPO-AS1 在 BCa 中的生物学作用和分子机制，TMPO-AS1 可能被鉴定为 BCa 患者的新治疗靶点。
