Long noncoding RNA PVT1-214 promotes proliferation and invasion of colorectal cancer by stabilizing Lin28 and interacting with miR-128 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-01

AUTHORS

Feng He, Zhi Song, Huacui Chen, Zhuanpeng Chen, Ping Yang, Wanglin Li, Zhi Yang, Tong Zhang, Fei Wang, Jianchang Wei, Fang Wei, Qiang Wang, Jie Cao

ABSTRACT

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. More... »

PAGES

164-179

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-018-0432-8

DOI

http://dx.doi.org/10.1038/s41388-018-0432-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105977934

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30076414


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