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长链非编码RNA SNHG1通过与TAp63相互作用调节锌指E盒结合同源框1的表达,并促进肺鳞状细胞癌的细胞转移和侵袭。

Long non-coding RNA SNHG1 regulates zinc finger E-box binding homeobox 1 expression by interacting with TAp63 and promotes cell metastasis and invasion in Lung squamous cell carcinoma.

作者信息

Zhang Hong-Yan, Yang Wei, Zheng Fu-Shuang, Wang Yi-Bei, Lu Ji-Bin

机构信息

Department of Thoracic Surgery, Shengjing Hospital of China Medical University, No.36 San Hao Street, Shenyang 110004, PR China.

Department of Thoracic Surgery, Shengjing Hospital of China Medical University, No.36 San Hao Street, Shenyang 110004, PR China.

出版信息

Biomed Pharmacother. 2017 Jun;90:650-658. doi: 10.1016/j.biopha.2017.03.104. Epub 2017 Apr 14.

DOI:10.1016/j.biopha.2017.03.104
PMID:28415044
Abstract

The long non-coding RNAs (lncRNAs) have been recently shown to participate in the progression of a variety of cancers. However, the biological role of lncRNAs and the underlying mechanisms in Lung squamous cell carcinoma (SCC) or lung adenocarcinoma (AD) remain unclear. Herein, we investigated expression of 5 lncRNAS (SNHG1, NCBP2-AS2, LINC01206, SOX2-OT and LINC01419) in SCC and AD tissues. SNHG1 was one of over-expressed lncRNAs in SCC tissues. Knockdown of SNHG1 significantly inhibited the proliferation, metastasis, invasive ability and induced apoptosis of SCC cells. Moreover, SNHG1 affected the expression of zinc finger E-box binding homeobox 1(ZEB1), which has also been observed to be up-regulated in SCC and to promote cell metastasis and invasion. Rather than direct interaction, SNHG1 regulated ZEB1expression by suppressing the activity of p63 TA isoform (TAp63), which is a repressor of ZEB1 and physically associates with SNHG1. Furthermore, SNHG1 promoted ZEB1 expression and promoted cell proliferation, metastasis, invasive but inhibited apoptosis of SCC cells via the TAp63/ZEB1 pathway. Taken together, our findings suggested that SNHG1 might play an oncogenic role in SCC through ZEB1 signaling pathway by inhibiting TAp63 and might serve as a valuable prognostic biomarker and therapeutic target for SCC patients.

摘要

长链非编码RNA(lncRNAs)最近已被证明参与多种癌症的进展。然而,lncRNAs在肺鳞状细胞癌(SCC)或肺腺癌(AD)中的生物学作用及潜在机制仍不清楚。在此,我们研究了5种lncRNAs(SNHG1、NCBP2-AS2、LINC01206、SOX2-OT和LINC01419)在SCC和AD组织中的表达。SNHG1是SCC组织中过表达的lncRNAs之一。敲低SNHG1可显著抑制SCC细胞的增殖、转移、侵袭能力并诱导其凋亡。此外,SNHG1影响锌指E盒结合同源框1(ZEB1)的表达,在SCC中ZEB1也被观察到上调,并促进细胞转移和侵袭。SNHG1并非直接相互作用,而是通过抑制p63 TA异构体(TAp63)的活性来调节ZEB1表达,TAp63是ZEB1的一种阻遏物,且与SNHG1存在物理关联。此外,SNHG1通过TAp63/ZEB1途径促进ZEB1表达,促进SCC细胞增殖、转移、侵袭,但抑制其凋亡。综上所述,我们的研究结果表明,SNHG1可能通过抑制TAp63,经由ZEB1信号通路在SCC中发挥致癌作用,并且可能作为SCC患者有价值的预后生物标志物和治疗靶点。

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