Long noncoding RNA LINC00239 inhibits ferroptosis in colorectal cancer by binding to Keap1 to stabilize Nrf2

Ferroptosis, a novel regulated cell death induced by iron-dependent lipid peroxidation, plays an important role in tumor development and drug resistance. Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumorigenesis remain elus...

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Vydáno v:Cell death & disease Ročník 13; číslo 8; s. 742 - 13
Hlavní autoři: Han, Yuying, Gao, Xiaoliang, Wu, Nan, Jin, Yirong, Zhou, He, Wang, Weijie, Liu, Hao, Chu, Yi, Cao, Jiayi, Jiang, Mingzuo, Yang, Suzhen, Shi, Yanting, Xie, Xin, Chen, Fulin, Han, Ying, Qin, Wen, Xu, Bing, Liang, Jie
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 29.08.2022
Springer Nature B.V
Nature Publishing Group
Témata:
101/58
13/109
13/51
14/19
38
38/1
45/15
45/91
631/67/1504/1885
631/80/82
96/95
Antibodies
Antitumor agents
Binding sites
Biochemistry
Biomedical and Life Sciences
Cancer
Cell Biology
Cell Culture
Cell death
Chemoresistance
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - pathology
Drug resistance
Ferroptosis
Ferroptosis - genetics
Humans
Immunology
Kelch-Like ECH-Associated Protein 1 - genetics
Kelch-Like ECH-Associated Protein 1 - metabolism
Life Sciences
Lipid peroxidation
Medical prognosis
NF-E2-Related Factor 2 - metabolism
Non-coding RNA
NRF2 protein
Nucleotides
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Transcriptomics
Tumorigenesis
Ubiquitination
Xenografts
ISSN:2041-4889, 2041-4889
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Shrnutí:Ferroptosis, a novel regulated cell death induced by iron-dependent lipid peroxidation, plays an important role in tumor development and drug resistance. Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumorigenesis remain elusive. Here we explored the transcriptomic profiles of lncRNAs in primary CRC tissues and corresponding paired adjacent non-tumor tissues by RNA-seq and found that LINC00239 was significantly overexpressed in colorectal cancer tissues. Abnormally high expression of LINC00239 predicts poorer survival and prognosis in colorectal cancer patients. Concurrently, we elucidated the role of LINC00239 as a tumor-promoting factor in CRC through in vitro functional studies and in vivo tumor xenograft models. Importantly, overexpression of LINC00239 decreased the anti-tumor activity of erastin and RSL3 by inhibiting ferroptosis. Collectively, these data suggest that LINC00239 plays a novel and indispensable role in ferroptosis by nucleotides 1–315 of LINC00239 to interact with the Kelch domain (Nrf2-binding site) of Keap1, inhibiting Nrf2 ubiquitination and increasing Nrf2 protein stability. Considering the recurrence and chemoresistance constitute the leading cause of death in colorectal cancer (CRC), ferroptosis induction may be a promising therapeutic strategy for CRC patients with low LINC00239 expression.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-022-05192-y