In:
PLOS Biology, Public Library of Science (PLoS), Vol. 20, No. 11 ( 2022-11-28), p. e3001885-
Abstract:
N6-methyladenosine (m6A) modification of RNA regulates normal and cancer biology, but knowledge of its function on long noncoding RNAs (lncRNAs) remains limited. Here, we reveal that m6A regulates the breast cancer-associated human lncRNA HOTAIR. Mapping m6A in breast cancer cell lines, we identify multiple m6A sites on HOTAIR, with 1 single consistently methylated site (A783) that is critical for HOTAIR-driven proliferation and invasion of triple-negative breast cancer (TNBC) cells. Methylated A783 interacts with the m6A “reader” YTHDC1, promoting chromatin association of HOTAIR, proliferation and invasion of TNBC cells, and gene repression. A783U mutant HOTAIR induces a unique antitumor gene expression profile and displays loss-of-function and antimorph behaviors by impairing and, in some cases, causing opposite gene expression changes induced by wild-type (WT) HOTAIR. Our work demonstrates how modification of 1 base in an lncRNA can elicit a distinct gene regulation mechanism and drive cancer-associated phenotypes.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001885
DOI:
10.1371/journal.pbio.3001885.g001
DOI:
10.1371/journal.pbio.3001885.g002
DOI:
10.1371/journal.pbio.3001885.g003
DOI:
10.1371/journal.pbio.3001885.g004
DOI:
10.1371/journal.pbio.3001885.g005
DOI:
10.1371/journal.pbio.3001885.g006
DOI:
10.1371/journal.pbio.3001885.g007
DOI:
10.1371/journal.pbio.3001885.s001
DOI:
10.1371/journal.pbio.3001885.s002
DOI:
10.1371/journal.pbio.3001885.s003
DOI:
10.1371/journal.pbio.3001885.s004
DOI:
10.1371/journal.pbio.3001885.s005
DOI:
10.1371/journal.pbio.3001885.s006
DOI:
10.1371/journal.pbio.3001885.s007
DOI:
10.1371/journal.pbio.3001885.s008
DOI:
10.1371/journal.pbio.3001885.s009
DOI:
10.1371/journal.pbio.3001885.s010
DOI:
10.1371/journal.pbio.3001885.s011
DOI:
10.1371/journal.pbio.3001885.s012
DOI:
10.1371/journal.pbio.3001885.s013
DOI:
10.1371/journal.pbio.3001885.s014
DOI:
10.1371/journal.pbio.3001885.s015
DOI:
10.1371/journal.pbio.3001885.s016
DOI:
10.1371/journal.pbio.3001885.s017
DOI:
10.1371/journal.pbio.3001885.s018
DOI:
10.1371/journal.pbio.3001885.s019
DOI:
10.1371/journal.pbio.3001885.s020
DOI:
10.1371/journal.pbio.3001885.s021
DOI:
10.1371/journal.pbio.3001885.r001
DOI:
10.1371/journal.pbio.3001885.r002
DOI:
10.1371/journal.pbio.3001885.r003
DOI:
10.1371/journal.pbio.3001885.r004
DOI:
10.1371/journal.pbio.3001885.r005
DOI:
10.1371/journal.pbio.3001885.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2126773-X
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