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长链非编码RNA ZFAS1通过HGF/c-Met途径靶向RALY,海绵化miR-193a-3p以调节肝母细胞瘤生长。

The Long Non-coding RNA ZFAS1 Sponges miR-193a-3p to Modulate Hepatoblastoma Growth by Targeting RALY via HGF/c-Met Pathway.

作者信息

Cui Xichun, Wang Zhifang, Liu Liwen, Liu Xin, Zhang Dandan, Li Jianhao, Zhu Jianming, Pan Juntao, Zhang Da, Cui Guangying

机构信息

Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Cell Dev Biol. 2019 Nov 8;7:271. doi: 10.3389/fcell.2019.00271. eCollection 2019.

Abstract

Hepatoblastoma (HB) is the most common and aggressive malignant hepatic neoplasm in childhood and the therapeutic outcomes remain undesirable due to its recurrence and metastasis. Recently, long non-coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) has been reported to be an oncogenic gene in multiple cancers. However, the expression status and specific role of ZFAS1 involved in cancer progression of human HB remain unknown. This study aimed to identify the role of ZFAS1/miR-193a-3p/RALY axis in the development of HB. Here we showed that the expression of ZFAS1 was significantly upregulated in both HB tissues and cell lines. High ZFAS1 expression was significantly associated with aggressive tumor phenotypes and poorer overall survival in HB. and function assays indicated that silencing of ZFAS1 significantly suppressed HB cell proliferation and invasion. Furthermore, miR-193a-3p was identified to be the target of ZFAS1. Subsequently, RALY was confirmed to be regulated by miR-193a-3p/ZFAS1 axis. Mechanistically, our results indicated that the ZFAS1 participated to the progression of HB via regulating the HGF/c-Met signaling. Collectively, these data demonstrated that ZFAS1 acted as an oncogene to promote initiation and progression of HB by regulating miR-193a-3p/RALY (RALY Heterogeneous Nuclear Ribonucleoprotein) axis via HGF/c-Met Pathway, which provides an efficient marker and new therapeutic target for HB.

摘要

肝母细胞瘤(HB)是儿童期最常见且侵袭性最强的恶性肝脏肿瘤,由于其复发和转移,治疗效果仍不理想。最近,长链非编码RNA(lncRNA)锌指反义1(ZFAS1)已被报道为多种癌症中的致癌基因。然而,ZFAS1在人类HB癌症进展中的表达状态和具体作用仍不清楚。本研究旨在确定ZFAS1/miR-193a-3p/RALY轴在HB发生发展中的作用。在此我们发现,ZFAS1在HB组织和细胞系中的表达均显著上调。ZFAS1高表达与HB中侵袭性肿瘤表型及较差的总生存率显著相关。功能分析表明,沉默ZFAS1可显著抑制HB细胞的增殖和侵袭。此外,miR-193a-3p被确定为ZFAS1的靶标。随后,RALY被证实受miR-193a-3p/ZFAS1轴调控。机制上,我们的结果表明ZFAS1通过调节HGF/c-Met信号通路参与HB的进展。总体而言,这些数据表明ZFAS1作为一种致癌基因,通过HGF/c-Met途径调节miR-193a-3p/RALY(RALY异质核糖核蛋白)轴,促进HB的起始和进展,这为HB提供了一个有效的标志物和新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04e9/6856658/f9d82cbb0ffa/fcell-07-00271-g001.jpg

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