LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer
Posted on 2019-12-03 - 04:41
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.
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Wang, Yun; Lu, Jia-Huan; Wu, Qi-Nian; Jin, Ying; Wang, De-Shen; Chen, Yan-Xing; et al. (2019). LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4766810.v1
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AUTHORS (19)
YW
Yun Wang
JL
Jia-Huan Lu
QW
Qi-Nian Wu
YJ
Ying Jin
DW
De-Shen Wang
YC
Yan-Xing Chen
JL
Jia Liu
XL
Xiao-Jing Luo
QM
Qi Meng
HP
Heng-Ying Pu
YW
Ying-Nan Wang
PH
Pei-Shan Hu
ZL
Ze-Xian Liu
ZZ
Zhao-Lei Zeng
QZ
Qi Zhao
RD
Rong Deng
XZ
Xiao-Feng Zhu
HJ
Huai-Qiang Ju
RX
Rui-Hua Xu