In:
Cancer Science, Wiley, Vol. 114, No. 9 ( 2023-09), p. 3649-3665
Abstract:
As an epitranscriptomic modulation manner, N 6 ‐methyladenosine (m 6 A) modification plays important roles in various diseases, including hepatocellular carcinoma (HCC). m 6 A modification affects the fate of RNAs. The potential contributions of m 6 A to the functions of RNA still need further investigation. In this study, we identified long noncoding RNA FAM111A‐DT as an m 6 A‐modified RNA and confirmed three m 6 A sites on FAM111A‐DT. The m 6 A modification level of FAM111A‐DT was increased in HCC tissues and cell lines, and increased m 6 A level was correlated with poor survival of HCC patients. m 6 A modification increased the stability of FAM111A‐DT transcript, whose expression level showed similar clinical relevance to that of the m 6 A level of FAM111A‐DT. Functional assays found that only m 6 A‐modified FAM111A‐DT promoted HCC cellular proliferation, DNA replication, and HCC tumor growth. Mutation of m 6 A sites on FAM111A‐DT abolished the roles of FAM111A‐DT. Mechanistic investigations found that m 6 A‐modified FAM111A‐DT bound to FAM111A promoter and also interacted with m 6 A reader YTHDC1, which further bound and recruited histone demethylase KDM3B to FAM111A promoter, leading to the reduction of the repressive histone mark H3K9me2 and transcriptional activation of FAM111A . The expression of FAM111A was positively correlated with the m 6 A level of FAM111A‐DT, and the expression of methyltransferase complex, YTHDC1, and KDM3B in HCC tissues. Depletion of FAM111A largely attenuated the roles of m 6 A‐modified FAM111A‐DT in HCC. In summary, the m 6 A‐modified FAM111A‐DT/YTHDC1/KDM3B/FAM111A regulatory axis promoted HCC growth and represented a candidate therapeutic target for HCC.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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