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

Oncogene volume 38, pages 164–179 (2019)Cite this article

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A Correction to this article was published on 09 November 2021

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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.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (Grant no. 8187101464, 81600654 and 81600862); the Guangdong Natural Science Foundation (Grant no. 2017A030311035, 2016A030313490 and 2016A030310227); the Fundamental Research Funds for the Central Universities (Grant no. XZYXD2175080); and the Guangdong Provincial Department of Science and Technology (Grant no. 2017A020215146); Guangzhou Science Technology and Innovation Commission (Grant no. 201805010003); and US National Institutes of Health (NIH) grant R01 HL136507.

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  1. These authors contributed equally: Feng He, Zhi Song, Huacui Chen.

Authors and Affiliations

  1. Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, 510180, China

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

  2. Department of Nephrology, Guangzhou First People’s Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, 510180, China

    Feng He

  3. Department of Pathology, Yale University School of Medicine, New Haven, 06520, CT, USA

    Feng He, Zhi Song & Huacui Chen

  4. Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China

    Zhi Song

  5. Department of General Surgery, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, 510180, China

    Huacui Chen & Jie Cao

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  1. Feng He
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Correspondence to Jie Cao.

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Accession numbers: Microarray data have been deposited in the Gene Expression Omnibus database (accession number GSE109454).

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He, F., Song, Z., Chen, H. et al. Long noncoding RNA PVT1-214 promotes proliferation and invasion of colorectal cancer by stabilizing Lin28 and interacting with miR-128. Oncogene 38, 164–179 (2019). https://doi.org/10.1038/s41388-018-0432-8

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