LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer
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 expres...
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BMC
2019-12-01
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Series: | Molecular Cancer |
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Online Access: | https://doi.org/10.1186/s12943-019-1105-0 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer Molecular Cancer Autophagy CRC IGF2BP2 LINRIS MYC |
author_facet |
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 |
author_sort |
Yun Wang |
title |
LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer |
title_short |
LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer |
title_full |
LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer |
title_fullStr |
LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer |
title_full_unstemmed |
LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer |
title_sort |
lncrna linris stabilizes igf2bp2 and promotes the aerobic glycolysis in colorectal cancer |
publisher |
BMC |
series |
Molecular Cancer |
issn |
1476-4598 |
publishDate |
2019-12-01 |
description |
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. |
topic |
Autophagy CRC IGF2BP2 LINRIS MYC |
url |
https://doi.org/10.1186/s12943-019-1105-0 |
work_keys_str_mv |
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doaj-cd254d1cc795495d9725359a49bd532b2020-12-06T12:31:08ZengBMCMolecular Cancer1476-45982019-12-0118111810.1186/s12943-019-1105-0LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancerYun Wang0Jia-Huan Lu1Qi-Nian Wu2Ying Jin3De-Shen Wang4Yan-Xing Chen5Jia Liu6Xiao-Jing Luo7Qi Meng8Heng-Ying Pu9Ying-Nan Wang10Pei-Shan Hu11Ze-Xian Liu12Zhao-Lei Zeng13Qi Zhao14Rong Deng15Xiao-Feng Zhu16Huai-Qiang Ju17Rui-Hua Xu18State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer CenterAbstract 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.https://doi.org/10.1186/s12943-019-1105-0AutophagyCRCIGF2BP2LINRISMYC |