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Compound
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Target Concepts:
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Query: UMLS:C0345904 (
liver cancer
)
15,188
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
N6-Methyladenosine (m
6
A) modification has been implicated in the progression of several cancers. We reveal that during epithelial-mesenchymal transition (EMT), one important step for cancer cell metastasis, m
6
A modification of mRNAs increases in cancer cells. Deletion of methyltransferase-like 3 (METTL3) down-regulates m
6
A, impairs the migration, invasion and EMT of cancer cells both in vitro and in vivo. m
6
A-sequencing and functional studies confirm that Snail, a key transcription factor of EMT, is involved in m
6
A-regulated EMT. m
6
A in Snail CDS, but not 3'UTR, triggers polysome-mediated translation of Snail mRNA in cancer cells. Loss and gain functional studies confirm that
YTHDF1
mediates m
6
A-increased translation of Snail mRNA. Moreover, the upregulation of METTL3 and
YTHDF1
act as adverse prognosis factors for overall survival (OS) rate of
liver cancer
patients. Our study highlights the critical roles of m
6
A on regulation of EMT in cancer cells and translation of Snail during this process.
...
PMID:RNA m
6
A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail. 3106 16
The development of next-generation sequencing technology and the discovery of specific antibodies targeting chemically modified nucleotides have paved the way for a new era of epitranscriptomics. Cellular RNA is known to dynamically and reversibly undergo different chemical modifications after transcription, such as N
6
-methyladenosine (m
6
A), N
1
-methyladenosine, N
6
,2'-O-dimethyladenosine, 5-methylcytosine, and 5-hydroxymethylcytidine, whose identity and location comprise the field of epitranscriptomics. Dynamic post-transcriptional modifications determine the fate of target RNAs by regulating various aspects of their processing, including RNA export, transcript processing, splicing, and degradation. The most abundant internal mRNA modification in eukaryotic cells is m
6
A, which exhibits essential roles in physiological processes, such as embryogenesis, carcinogenesis, and neurogenesis. m
6
A is deposited by the m
6
A methyltransferase complex (composed of METTL3/14/16, WTAP, KIAA1429, and RBM15/15B), erased by demethylases (FTO and ALKBH5), and recognised by binding proteins (e.g.,
YTHDF1
/2/3, YTHDC1/2, IGF2BP1/2/3). The liver is the largest digestive and metabolic organ, and m
6
A modifications play unique roles in critical physiological hepatic functions and various liver diseases. This review focuses on the biological roles of m
6
A RNA methylation in lipid metabolism, viral hepatitis, non-alcoholic fatty liver disease,
liver cancer
, and tumour metastasis. In addition, we summarise the existing inhibitors targeting m
6
A regulators and discuss the potential of modulating m
6
A modifications as a therapeutic strategy.
...
PMID:Epitranscriptomics in liver disease: Basic concepts and therapeutic potential. 3233 Jun 3
Studies on biological functions of N
6
-methyladenosine (m
6
A) modification in mRNA have sprung up in recent years. We find m
6
A can positively regulate the glycolysis of cancer cells. Specifically, m
6
A-sequencing and functional studies confirm that pyruvate dehydrogenase kinase 4 (PDK4) is involved in m
6
A regulated glycolysis and ATP generation. The m
6
A modified 5'UTR of PDK4 positively regulates its translation elongation and mRNA stability via binding with
YTHDF1
/eEF-2 complex and IGF2BP3, respectively. Targeted specific demethylation of PDK4 m
6
A by dm
6
ACRISPR system can significantly decrease the expression of PDK4 and glycolysis of cancer cells. Further, TATA-binding protein (TBP) can transcriptionally increase the expression of Mettl3 in cervical cancer cells via binding to its promoter. In vivo and clinical data confirm the positive roles of m
6
A/PDK4 in tumor growth and progression of cervical and
liver cancer
. Our study reveals that m
6
A regulates glycolysis of cancer cells through PDK4.
...
PMID:N
6
-methyladenosine regulates glycolysis of cancer cells through PDK4. 3244 98
