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TMPO-AS1/miR-98-5p/EBF1 feedback loop contributes to the progression of bladder cancer.
The International Journal of Biochemistry & Cell Biology ( IF 4 ) Pub Date : 2020-02-19 , DOI: 10.1016/j.biocel.2020.105702
Hua Luo 1 , Lu Yang 2 , Chen Liu 3 , Xiaobo Wang 3 , Qiang Dong 2 , Liangren Liu 2 , Qiang Wei 2
Affiliation  

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.



中文翻译:

TMPO-AS1 / miR-98-5p / EBF1反馈回路有助于膀胱癌的发展。

如许多研究报道的那样,长的非编码RNA(lncRNA)对调节肿瘤的发展起着重要作用。LncRNA TMPO反义RNA 1(TMPO-AS1)已被证实与几种癌症的发生有关。但是,其临床意义在膀胱癌(BCa)中仍然未知。在这项研究中,TMPO-AS1在BCa组织和细胞系中高表达,并且TMPO-AS1预后不良。此外,TMPO-AS1促进细胞生长。另外,TMPO-AS1还促进了BCa细胞的迁移和侵袭。从机制上讲,BCa细胞中过表达的EBF转录因子1(EBF1)被证实可以促进TMPO-AS1的转录。后来,我们发现TMPO-AS1是一种细胞质RNA,可以吞噬miR-98-5p。除了,证实EBF1是miR-98-5p的靶基因,并且在表达水平上与miR-98-5p负相关。根据救援实验的结果,我们观察到EBF1过表达恢复了TMPO-AS1沉默对BCa发育的抑制作用。我们的研究是第一个揭示TMPO-AS1在BCa中的生物学作用和分子机制的研究,而TMPO-AS1可能被确定为BCa患者的新治疗靶标。

更新日期:2020-02-19
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