Long noncoding RNA PVT1-214 promotes proliferation and invasion of colorectal cancer by stabilizing Lin28 and interacting with miR-128.
Long noncoding RNA PVT1-214 promotes proliferation and invasion of colorectal cancer by stabilizing Lin28 and interacting with miR-128.
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长非编码RNA PVT1-214通过稳定Lin28并与miR-128相互作用促进结直肠癌的增殖和侵袭
DOI：
10.1038/s41388-018-0432-8
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发表时间：
2019-01
期刊：
影响因子：
8
通讯作者：
Cao J
中科院分区：
文献类型：
--
作者：
He F;Song Z;Chen H;Chen Z;Yang P;Li W;Yang Z;Zhang T;Wang F;Wei J;Wei F;Wang Q;Cao J
长链非编码rna （lncRNAs）与人类癌症有关，但其作用机制在很大程度上是未知的。在这项研究中，我们通过微阵列表达谱研究了导致结直肠癌（CRC）的lncRNA改变。在这里，我们报告了CRC相关的lncRNA PVT1-214是CRC发生和进展的关键调节因子；PVT1-214高表达患者生存期较短，预后较差。体外和体内对PVT1-214作用的研究揭示了一个复杂的综合表型，影响细胞生长、茎样特性、迁移和侵袭。此外，通过RNA下拉和质谱分析，我们发现Lin28（也称为Lin28A）是一种高度保守的RNA结合蛋白，与PVT1-214相关。引人注目的是，我们发现PVT1-214不仅通过稳定Lin28来上调CRC细胞中Lin28蛋白的表达，而且还通过竞争miR-128的结合参与了与Lin28 mRNA的串扰，从而施加了额外水平的转录后调控。此外，我们进一步发现PVT1-214抑制let-7家族mirna的表达，而这种抑制被Lin28敲除。综上所述，我们的研究结果支持PVT1-214/Lin28/let-7轴作为CRC发病机制的关键调节因子的模型，这可能为CRC治疗发展模拟一个新的方向。
Long noncoding RNAs (lncRNAs) are implicated in human cancer, but their mechanisms of action are largely unknown. In this study, we investigated lncRNA alterations that contribute to colorectal cancer (CRC) through microarray expression profiling in CRC patient samples. Here, we report that the CRC-associated lncRNA PVT1-214 is a key regulator of CRC development and progression; patients with high PVT1-214 expression had a shorter survival and poorer prognosis. In vitro and in vivo investigation of the role of PVT1-214 revealed a complex integrated phenotype affecting cell growth, stem-like properties, migration, and invasion. Furthermore, using RNA pull-down and mass spectrometry, we found that Lin28 (also known as Lin28A), a highly conserved RNA-binding protein, is associated with PVT1-214. Strikingly, we found that PVT1-214 not only upregulated Lin28 protein expression in CRC cells by stabilizing Lin28, but also participated in crosstalk with Lin28 mRNA through competition for miR-128 binding, imposing an additional level of post-transcriptional regulation. In addition, we further show that PVT1-214 repressed expression of let-7 family miRNAs, which was abrogated by Lin28 knockdown. Taken together, our findings support a model in which the PVT1-214/Lin28/let-7 axis serves as a critical regulator of CRC pathogenesis, which may simulate a new direction for CRC therapeutic development.
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影响因子：
11.2
作者：
Di Cecilia S;Zhang F;Sancho A;Li S;Aguiló F;Sun Y;Rengasamy M;Zhang W;Del Vecchio L;Salvatore F;Walsh MJ
通讯作者：
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影响因子：
8.8
作者：
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64.8
作者：
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影响因子：
64.5
作者：
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影响因子：
11.2
作者：
Ma, Ming-zhe;Zhang, Yan;Quan, Zhi-wei
通讯作者：
Quan, Zhi-wei