The TWIST1-centered competing endogenous RNA network promotes proliferation, invasion, and migration of lung adenocarcinoma
The TWIST1-centered competing endogenous RNA network promotes proliferation, invasion, and migration of lung adenocarcinoma
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以TWIST1为中心的竞争性内源RNA网络促进肺腺癌的增殖、侵袭和迁移
DOI：
10.1038/s41389-019-0167-6
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发表时间：
2019-10-23
期刊：
影响因子：
6.2
通讯作者：
Jiang, Feng
中科院分区：
文献类型：
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作者：
Xia, Wenjie;Mao, Qixing;Jiang, Feng
提出的竞争内源RNA(CERNA)机制表明，不同的RNA物种，包括编码蛋白质的信使RNA和非编码RNA，如长的非编码RNA、伪基因和环状RNA，可以通过竞争与共享的microRNAs结合来相互通信。CENA网络(CeRNET)与肿瘤的发展密切相关，近年来已成为研究热点。到目前为止，非编码RNA在Cerna串扰中的作用受到了更多的关注。然而，编码转录本比非编码RNA更丰富、更强大，构成了miRNA靶标的大部分。在本研究中，我们构建了一个与mRNA相关的肺腺癌CERNET(LUAD)，并确定了突出的以Twist1为中心的CERNET，它招募SLC12A5和ZFHX4作为其ceRNAs。我们发现Twist1/SLC12A5/ZFHX4在LUAD中均表达上调，且与预后不良相关。SLC12A5和ZFHX4促进体内和体外的增殖、迁移和侵袭，它们的作用分别被miR-194-3p和miR-514a-3p逆转。我们进一步验证了SLC12A5和ZFHX4通过作为ceRNAs影响Twist1的功能。综上所述，我们为LUAD构建了一个与mRNA相关的ceRNET，并突出了众所周知的癌基因Twist1。证实SLC12A5和ZFHX4通过CERNA机制调节Twist1的表达，从而发挥其致癌作用。
The proposed competing endogenous RNA (ceRNA) mechanism suggested that diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs could communicate with each other by competing for binding to shared microRNAs. The ceRNA network (ceRNET) is involved in tumor progression and has become a hot research topic in recent years. To date, more attention has been paid to the role of non-coding RNAs in ceRNA crosstalk. However, coding transcripts are more abundant and powerful than non-coding RNAs and make up the majority of miRNA targets. In this study, we constructed a mRNA-mRNA related ceRNET of lung adenocarcinoma (LUAD) and identified the highlighted TWIST1-centered ceRNET, which recruits SLC12A5 and ZFHX4 as its ceRNAs. We found that TWIST1/SLC12A5/ZFHX4 are all upregulated in LUAD and are associated with poorer prognosis. SLC12A5 and ZFHX4 facilitated proliferation, migration, and invasion in vivo and in vitro, and their effects were reversed by miR-194–3p and miR-514a-3p, respectively. We further verified that SLC12A5 and ZFHX4 affected the function of TWIST1 by acting as ceRNAs. In summary, we constructed a mRNA-mRNA related ceRNET for LUAD and highlighted the well-known oncogene TWIST1. Then we verified that SLC12A5 and ZFHX4 exert their oncogenic function by regulating TWIST1 expression through a ceRNA mechanism.