Liu Jing, Huang Shimei, Liao Xin, Chen Zhongsheng, Li Lianghe, Yu Lei, Zhan Wei, Li Rui
Imaging Department, Affiliated Hospital of Guizhou Medical University, Guiyang, People's Republic of China.
Forensic Clinical Teaching and Research Office, Guizhou Medical University, Guiyang, People's Republic of China.
Onco Targets Ther. 2021 Jan 13;14:367-378. doi: 10.2147/OTT.S272895. eCollection 2021.
Ewing sarcoma-associated transcript 1 () has been reported to be a pivotal modulator in a series of cancers. However, the function of in colorectal cancer (CRC) has not been elaborated. This study aimed to explore the role of in CRC progression and the underlying mechanisms.
The expression patterns of , and were examined by qCRCR. Si-EWSAT1 was transfected to study the effects of on cell proliferation and metastasis. Rescue experiments were performed to investigate the underlying mechanisms in vitro. Xenograft models were used to evaluate the role of in vivo.
We found that was highly expressed in CRC tissues and cell lines and associated with poor overall survival. In vitro, knockdown of suppressed the cell proliferation, migration and invasion. Moreover, miR-326 was found to be a target of , and inhibitor could partially reverse the effects on CRC cell progression induced by si-EWSAT1. Subsequently, we validated as a vital downstream target for , and positively regulated via in vitro. In addition, these findings were confirmed by in vivo experiments.
Taken together, the data showed that promoted CRC progression via targeting pathway, which might provide a novel therapeutic target for CRC treatment.
据报道,尤因肉瘤相关转录本1(EWSAT1)在一系列癌症中是关键调节因子。然而,EWSAT1在结直肠癌(CRC)中的功能尚未阐明。本研究旨在探讨EWSAT1在CRC进展中的作用及其潜在机制。
通过qCRCR检测EWSAT1、miR-326和ZEB1的表达模式。转染Si-EWSAT1以研究EWSAT1对细胞增殖和转移的影响。进行挽救实验以体外研究潜在机制。使用异种移植模型在体内评估EWSAT1的作用。
我们发现EWSAT1在CRC组织和细胞系中高表达,且与总体生存率差相关。在体外,敲低EWSAT1可抑制细胞增殖、迁移和侵袭。此外,发现miR-326是EWSAT1的靶标,miR-326抑制剂可部分逆转si-EWSAT1对CRC细胞进展的影响。随后,我们验证ZEB1是EWSAT1的重要下游靶标,且EWSAT1在体外通过miR-326正向调节ZEB1。此外,体内实验证实了这些发现。
综上所述,数据表明EWSAT1通过靶向miR-326/ZEB1途径促进CRC进展,这可能为CRC治疗提供新的治疗靶点。