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Tumor Discovery RNA-protein complexes deregulated in cancer

Table 5. m6A modification: Role of ncRNA interactions with m6A writers, readers, and erasers
lncRNA Interaction Modified Effect References
FEZF1-AS1 IGF2BP1 sequestration m6A Apoptosis 195
DARS1-AS1 METTL3-METTL14 m6A Proliferation 196
THOR Readers YTHDF1 and YTHDF2 m6A Oncogenesis 197
LNCAROD METTL3-METTL14 m6A Prevents YBX1 degradation 198
GAS5 Reader YTHDF3 m6A GAS5 degradation 199
LINC021 IGF2BP2 m6A MSX1 stability 200
LINC0047 METTL3 m6A PTEN-m6A degradation 125
CASC11 ALKBH5 m6A Decrease in m6A UBE2T 200
NEAT1_2 ALKBH5, YTHDF2 m6A Destabilize mRNA 201,202
PVT1 Silencing ALKBH5 m6A Decrease levels 58
LEAWBIH YTHDC1 m6A Recruits H3K9me2 demethylase KDM3B 203
MALAT1 The serine/arginine-rich splicing factor m6A lncRNA m6A methylation 204
TRA2A forms a complex with writers
METTL14, RBMX, KIAA1429
LINC00022 FTO m6A Block degradation by YTHDF2 205
DANCR IGF2BP2 m6A Stabilized DANCR 206
circARHGAP35/ METTL3, HNRNPL m6A Promotes its translation, producing an 102
circDLC1 oncogenic protein
circDDIT4 METTL3-WTAP m6A Suppresses anoctamin (ANO7) binding to 189
ELAVL1/HuR, reduces PC progression
circRBM33 METTL3/YTHDC1 m6A RNA stability, abdominal aortic aneurysm 207
circ0049271 WTAP m6A IGF2BP3 binding, regulation of the TGF-b/ 208
SMAD signal, and promotion of EMT in gastric
cancer
circPTPRA, circNSUN, WTAP writer complex, IGF2BP1 m6A Cytoplasmic export and formation of protein 209
circ1662, circMEG3 binding, recruitment of YTHDF3 and ternary complexes
YTHDC1
circMARK2 METTL3 m6A Cytoplasmic export, Lin28B stabilization, Wilms 210
tumor progression
Note: An extensive database (http://www.xjtlu.edu.cn/biologicalsciences/m7ghub) is available as a tool to check RNA modifications.
Abbreviations: FTO: Fat mass and obesity; ALHB1: AlkB homolog protein 5; IGF2BP1: Insulin-like growth factor mRNA-binding protein 1;
METTL3: Methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit; CircARHGAP35/CircDLC1: Rho GTPase activating
protein 35 circular RNA; CircDDIT4: Damage inducible transcript 4 circular RNA; CircPPTRA; Protein tyrosine phosphatase receptor type A
circular RNA; DARS1-AS1: Aspartyl-tRNA synthetase, antisense; FEZF1-AS: FEZ family zinc finger1, antisense; GAS5: Growth arrest specific 5;
LNCAROD: LncRNA activating regulator of DKK1; DANCR: Differentiation antagonizing non-protein coding RNA; LEAWBIH: Long noncoding
RNA epigenetically activating Wnt/β-catenin signaling in HCC.

activator, have also been identified. 191,215 New studies vesicle-like nanoparticles encapsulating YTHDF1-siRNA
are investigating the role of m7G modification in cancer enhanced immune responses and improved anti-PD-1
through METTL1 activity, with efficient inhibitors therapy outcomes in vivo. 223
undergoing testing. 218
ONC213 suppressed mitochondrial respiration,
Studies have also focused on inhibitors and activators elevated α-ketoglutarate by inhibiting α-ketoglutarate
of m6A readers. IGF2BP1 and IGF2BP2 inhibitors dehydrogenase (αKGDH), and exhibited potent
have shown antiproliferative effects. 219-222 For instance, antileukemia activity with minimal toxicity. ALK‐04 is a
SU056, an azopodophyllotoxin-derived small molecule, selective ALKBH5 inhibitor. 220
effectively inhibits IGF2BP2, promoting apoptosis and
RNA degradation while reducing splicing pathways, with Several classes of FTO inhibitors have been developed
224
inhibitory effects in ovarian, lung, and breast cancers to target m6A erasers, including metal-chelating
and AML. Silencing the YTHDF1 m6A reader using inhibitors, substrate-competitive inhibitors, and various
219
Volume 3 Issue 4 (2024) 15 doi: 10.36922/td.4657