Energy stress-induced linc01564 activates the serine synthesis pathway and facilitates hepatocellular carcinogenesis

Cancer cells undergo metabolic adaption to sustain their survival and growth under metabolic stress conditions, yet the underlying mechanism remains largely unclear. It is also not known if lncRNAs contribute to this metabolic adaption of cancer cells. Here we show that linc01564 is induced in respo...

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Bibliographic Details
Published in:Oncogene 2021-04, Vol.40 (16), p.2936-2951
Main Authors: Zhang, Guang, Yang, Yang, Hu, Hao, Liu, Kaiyue, Li, Bingyan, Zhu, Yu, Wang, Zhongyu, Wu, Qingfa, Mei, Yide
Format: Article
Language:English
Subjects:
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Activating transcription factor 4
Apoptosis
Cancer
Carcinogenesis
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Cell Biology
Cell survival
Hepatocellular carcinoma
Human Genetics
Humans
Internal Medicine
Liver cancer
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Medicine
Medicine & Public Health
Metabolism
Oncology
RNA, Long Noncoding - metabolism
Serine
Serine - metabolism
Transfection
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Summary:Cancer cells undergo metabolic adaption to sustain their survival and growth under metabolic stress conditions, yet the underlying mechanism remains largely unclear. It is also not known if lncRNAs contribute to this metabolic adaption of cancer cells. Here we show that linc01564 is induced in response to glucose deprivation by the transcription factor ATF4. Linc01564 functions to facilitate hepatocellular carcinoma cell survival under glucose deprivation by activating the serine synthesis pathway. Mechanistically, linc01564 acts as a competing endogenous RNA for miR-107/103a-3p and attenuates the inhibitory effect of miR-107/103a-3p on PHGDH, the rate-limiting enzyme of the serine synthesis pathway, thereafter leading to increased PHGDH expression. Furthermore, linc01564 is able to promote hepatocellular carcinogenesis via PHGDH. Together, these findings suggest that linc01564 is an important player in the regulation of metabolic adaption of cancer cells and also implicate linc01564 as a potential therapeutic target for cancer.
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-021-01749-x