Previous studies have revealed the critical roles of the
N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) in
cancers, but the relationship between the oncogenic role of the
lncRNA THOR (a representative of
cancer/testis lncRNAs) and
m6A modification remains unclear. Here, we show that the internal
m6A modification of the
lncRNA THOR via an m6A-reader-dependent modality regulates the proliferation of
cancer cells. Our findings demonstrated that the loss of the
lncRNA THOR inhibits the proliferation, migration, and invasion of
cancer cells in vitro and in vivo. In addition,
m6A is highly enriched on
lncRNA THOR transcripts, which contain GA (
m6A) CA, GG (
m6A) CU, and UG (
m6A) CU sequence motifs. RIP-qRT-PCR and
RNA pull-down assay results revealed that the specific
m6A readers YTHDF1 and YTHDF2 can read the
m6A motifs and regulate the stability of the
lncRNA THOR (stabilization and decay). These m6A-dependent
RNA-
protein interactions can maintain the oncogenic role of the
lncRNA THOR. Collectively, these findings highlight the critical role of the
m6A modification in oncogenic
lncRNA THOR and reveal a novel
long non-coding RNA regulatory mechanism, providing a new way to explore
RNA epigenetic regulatory patterns in the future.