Table II.
Role of m6A in the initiation and progression of pancreatic cancer.
| Initiation factor | Oncogenicity/suppressor | Signaling or target | Effect | (Refs.) |
|---|---|---|---|---|
| METTL3 | Oncogenicity↑ | Proliferation↑ Metastasis↑ Invasion↑ |
(103) | |
| CSC-METTL3↑-miR-25-3p↑-PHLPP2↓-AKT-p70S6K↑ | Proliferation↑ Invasion↑ Metastasis↑ |
(84) | ||
| METTL3↑-NUCB1↓ | Proliferation↑ Chemical Resistance↑ |
(85) | ||
| Chemical Resistance↑ | (112) | |||
| METTL14 | Oncogenicity↑ | METTL14↑-PERP↑ | Proliferation↑ Apoptosis↓ Invasion↑ Metastasis↑ EMT↑ |
(86) |
| p65-METTL14↑-CDA↑ | Chemical Resistance↑ | (113) | ||
| METTL14↑- apoptosis; METTL14↑-mTOR-autophagy↓ | Apoptosis↓ Chemical Resistance↓ |
(114) | ||
| METTLE 16 | Suppressor↓ | METTL 16↓-P21 pathway↓ | Proliferation↓ | (87) |
| METTL5 | Oncogenicity↑ | METTL5↑-c-myc translation↑ | Proliferation↑ Invasion↑ Metastasis↑ |
(88) |
| WTAP | Oncogenicity↑ | WTAP↑-mRNA↑ | Metastasis↑ Chemical resistance↑ |
(104) |
| FTO | Suppressor↓ | FTO↓-YTHDF2-PJA2↓-Wnt signaling↑ | Proliferation↓ Invasion↓ Metastasis↓ |
(89) |
| FTO | Oncogenicity↑ | Proliferation↑ | (90) | |
| ALKBH5 | Suppressor↓ | ALKBH5↓-KCNK15-AS1↓ | Apoptosis↑ Invasion↓Metastasis↓ |
(92) |
| ALKBH5-↓lncRNA KCNK15-AS1↓-MDM2-REST ubiquitination↓-PTEN↓-AKT pathway↑ |
Apoptosis↑ invasion↓ metastasis↓ EMT↓ |
(93) | ||
| ALKBH5↓-PER1↓-ATM-CHK2-P53/CDC25C↓ | Proliferation↓ Invasion↓ Metastasis↓ |
(91) | ||
| ALKBH5↓-WIF-1↓-Wnt signaling↑ | Proliferation↓ Invasion↓ Metastasis↓ Chemical resistance↓ |
(94) | ||
| ALKBH5↓-FBXL5↓-degradation↓ | Apoptosis↑ | (95) | ||
| YTHDF2 | Oncogenicity↑ | YTHDF2↑-YAP↓ | Proliferation↑ Invasion↓ Metastasis↓ EMT↓ |
(105) |
| YTHDF3 | Oncogenicity↑ | YTHDF3↑-lncRNA DICER1-AS1↓-DICER1↓-maturation of miR-5586-5p↓ | Proliferation↑ Metastasis↑ Metabolism |
(110) |
| HNRNPA2B1 | Oncogenicity↑ | HNRNPA2B1-ERK/snail-E-cadherin↓N-cadherin and vimentin↑ | Invasion↑ EMT↑ | (106) |
| IGF2BP2 | Oncogenicity↑ | IGF2BP2↑-DANCR↑ | Proliferation↑ | (96) |
| IGF2BP2↑-mRNA GLUT1↑ | Proliferation↑ Metabolism | (111) | ||
| IGF2BP2↑- protein IMP2↑ |
Apoptosis↑ Metastasis↑ EMT↑ |
(107) | ||
| LINC00857 | Oncogenicity↑ | LINC00857↑-miR-150-5p↓-E2F3↑ | Proliferation↑ Apoptosis↓ |
(97) |
| LINC00261 | Suppressor↓ | LINC00261↓-IGF2BP1↑-c-Myc↑ | Proliferation↑ Apoptosis↓ Metabolism |
(98) |
| LINC00261↓-miR-222-3p/HIPK2/ | Proliferation↑ Apoptosis↓ Metabolism |
(98) | ||
| ERK↑-c-myc↑ | ||||
| rs7495 genetic variant | hnRNPC↑ | Proliferation↑ | (100) | |
| rs7495G allele-has-miR- | Proliferation↑ | (99) | ||
| 183-3p-hnRNPC↑ | ||||
| rs142933486 genetic variant | PIK3CB↑ | Proliferation↑ Metastasis↑ |
(101) | |
| CLK1↑ | METTL14exon 10skipping↓ | Metastasis↑ | (108) | |
| Cyclin L2exon6.3skipping↑ | Proliferation↑ | (108) | ||
| HNRNPC | Structural switch | TAF8L↓ | Metastasis↑ | (109) |
| TAF8S↑ | Metastasis↑ | (109) |
'↑' represents upregulation and '↓' represents downregulation. EMT, epithelial-mesenchymal transition; CSC, cigarette smoke condensate; NUCB1, nucleobindin 1; PERP, p53 effector related to PMP-22; PJA2, praja ring finger ubiquitin ligase 2; METTL, methyltransferase-like protein; WTAP, Wilms' tumor 1-associating protein; VIRMA, Vir-like m6A methyltransferase-associated; RBM15, RNA-binding motif protein 15; ZC3H13, zinc finger CCCH-type containing 13; CBLL1, Casitas B lineage lymphoma transforming sequence like protein 1; FTO, fat mass and obesity-associated protein; ALKBH5, alkB homolog 5, RNA demethylase; YTHDC, YT521-B homology domain-containing protein; HNRN, heterogeneous nuclear ribonucleoprotein; IGF2BPS, insulin-like growth factor-2 mRNA-binding proteins; YTHDF, YTH N6 methyl- adenosine RNA binding protein.