LncRNA RSU1P2 contributes to tumorigenesis by acting as a ceRNA against let-7a in cervical cancer cells.
LncRNA RSU1P2 contributes to tumorigenesis by acting as a ceRNA against let-7a in cervical cancer cells.
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DOI：
10.18632/oncotarget.10844
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发表时间：
2017-07-04
期刊：
影响因子：
--
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Liu Q;Guo X;Que S;Yang X;Fan H;Liu M;Li X;Tang H
长非编码RNA(Long Non-Coding RNAs，LncRNAs)可以在不同水平上调控基因表达，广泛参与多种生理和病理过程。新的证据表明，许多差异表达的lncRNAs参与了肿瘤的发生。然而，这些独特的RNA中的绝大多数的功能和表达调控却鲜为人知。在这里，我们发现LncRNA RAS抑制蛋白1假基因2(RSU1P2)在宫颈癌组织中表达上调，并具有促肿瘤作用。我们发现RSU1P2通过调节IGF1R、N-myc和EphA4的表达而发挥竞争内源性RNA(CerNA)的作用。这种调节机制是通过竞争共享的microRNA let-7a来实现的。这一竞争促进了宫颈癌细胞的恶性表型。转录因子N-myc通过激活RSU1P2的表达与RSU1P2形成正反馈环，从而增强其致癌能力。因此，RSU1P2的癌症选择性靶向可能会有很大的好处。
Long non-coding RNAs (lncRNAs) can regulate gene expression at different levels and are widely participate in various physiological and pathological processes. Emerging evidences suggests that a number of differentially expressed lncRNAs are involved in tumorigenesis. However, the function and expression regulation of a vast majority of these unique RNAs is little known. Here, we found that the lncRNA Ras suppressor protein 1 pseudogene 2 (RSU1P2) is upregulateded in cervical cancer tissues and has a tumour-promoting role. We revealed that RSU1P2 acts as a competitive endogenous RNA (ceRNA) through regulating the expression of IGF1R, N-myc and EphA4. The mechanism of this regulation is via competition for the shared microRNA let-7a. This competition promotes the malignant phenotype of cervical carcinoma cells. The transcription factor N-myc forms a positive feedback loop with RSU1P2 by in turn activating its expression, thereby enhancing its oncogenic capacity. Hence, cancer-selective targeting of RSU1P2 could have strong benefits.
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