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Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Colorectal Cancer | Research

LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer

Authors: Yun Wang, Jia-Huan Lu, Qi-Nian Wu, Ying Jin, De-Shen Wang, Yan-Xing Chen, Jia Liu, Xiao-Jing Luo, Qi Meng, Heng-Ying Pu, Ying-Nan Wang, Pei-Shan Hu, Ze-Xian Liu, Zhao-Lei Zeng, Qi Zhao, Rong Deng, Xiao-Feng Zhu, Huai-Qiang Ju, Rui-Hua Xu

Published in: Molecular Cancer | Issue 1/2019

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Abstract

Background

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and could be a potential therapeutic target.

Methods

We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo.

Results

LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N6-methyladenosine (m6A) ‘reader’. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models.

Conclusion

LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.
Appendix
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Metadata
Title
LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer
Authors
Yun Wang
Jia-Huan Lu
Qi-Nian Wu
Ying Jin
De-Shen Wang
Yan-Xing Chen
Jia Liu
Xiao-Jing Luo
Qi Meng
Heng-Ying Pu
Ying-Nan Wang
Pei-Shan Hu
Ze-Xian Liu
Zhao-Lei Zeng
Qi Zhao
Rong Deng
Xiao-Feng Zhu
Huai-Qiang Ju
Rui-Hua Xu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-1105-0

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