LAST, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote CCND1 mRNA stability in human cells

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Abstract

Cyclin D1 is a critical regulator of cell cycle progression and works at the G1 to S-phase transition. Here, we report the isolation and characterization of the novel c-Myc-regulated lncRNA LAST (LncRNA-Assisted Stabilization of Transcripts), which acts as a CCND1 mRNA stabilizer. Mechanistically, LAST was shown to cooperate with CNBP to bind to the 5′UTR of CCND1 mRNA to protect against possible nuclease targeting. In addition, data from CNBP RIP-seq and LAST RNA-seq showed that CCND1 mRNA might not be the only target of LAST and CNBP; three additional mRNAs were shown to be post-transcriptional targets of LAST and CNBP. In a xenograft model, depletion of LAST diminished and ectopic expression of LAST induced tumor formation, which are suggestive of its oncogenic function. We thus report a previously unknown lncRNA involved in the fine-tuned regulation of CCND1 mRNA stability, without which CCND1 exhibits, at most, partial expression.

Data availability

The following data sets were generated

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Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE106917).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE106917
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(2017) Identification of CNBP binding mRNA and the binding sites/motifs in HCT116 cells
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE106918).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE106918

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Article and author information

Author details

Limian Cao

School of Life Sciences, University of Science and Technology of China, Hefei, China

Competing interests
The authors declare that no competing interests exist.
Pengfei Zhang

School of Life Sciences, University of Science and Technology of China, Hefei, China

Competing interests
The authors declare that no competing interests exist.
Jinming Li

Translational Research Institute, Henan Provincial People's Hospital, Zhengzhou, China

Competing interests
The authors declare that no competing interests exist.
Mian Wu

School of Life Sciences, University of Science and Technology of China, Hefei, China

For correspondence
wumian@ustc.edu.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2714-0500

Funding

Ministry of Science and Technology of the People's Republic of China (2016YFC1302302)

Mian Wu

National Natural Science Foundation of China (81430065)

Mian Wu

National Natural Science Foundation of China (31371388)

Mian Wu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Studies on animals in this paper were conducted with approval from the Animal Research Ethics Committee of the University of Science and Technology of China (Permit Number: USTCACUC1701003).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.