From: Small RNA modifications: regulatory molecules and potential applications
Small RNA | Enzyme | Regulator network (↑ denotes upregulation, ↓ denotes downregulation) | Cellular function | Disease association | Reference |
---|---|---|---|---|---|
miR-375 | METTL14 | lncRNA UCA1 ↑ → METTL14↓ → pri-miR-375↑, miR-375↓ → SOX12↑ | Promotes cell proliferation and invasion but inhibits apoptosis | Breast cancer | [70] |
miR‐181b‐3p | FTO | FTO ↑→ miR‐181b‐3p ↓ → ARL5B ↑ | Promotes cell migration and tissue invasion | Breast cancer | [71] |
miR-221-3p | METTL3 | METTL3 ↑ → m6A-modified pri-miR-221-3p ↑, miR-221-3p ↑ → HIPK2 ↓ →Che-1 ↑ | Enhances drug resistance in adriamycin-resistant breast cancer cells | Breast cancer | [72] |
miR-374c-5p | Unknown | Cadmium treatment → m6A-modified pri-miR-374c ↓ → pri-miR-374c ↑, miR-374c-5p ↓ → GRM3 ↑ | Promotes cell proliferation and metastasis | Breast cancer | [73] |
miR-1246 | METTL3 | METTL3 ↑ → m6A-modified pri-miR-1246 ↑ → pri-miR-1246 ↓, miR-1246 ↑ → SPRED2 ↓ → activates RAF/MEK/ERK pathway | Promotes cancer cell metastasis | Colorectal cancer | [74] |
Let-7b-5p | METTL3 | Metformin stimulation-METTL3 ↑ → pri-Let-7b ↓, pre-Let-7b↑, Let-7b-5p ↑ → suppresses Notch signaling | Increases sensitivity to Osimertinib therapy in patients with cancer | Lung cancer | [75] |
miR-143-3p | METTL3 | METTL3 ↑ → m6A-modified pre-miR-143-3p ↑ → pre-miR-143-3p ↓, miR-143-3p ↑ → VASH1 ↓ | Triggers epithelial-mesenchymal transition (EMT) in a blood brain barrier model of ell invasion, as well as angiogenesis in the context of lung cancer | Lung cancer | [76] |
miR-106b | HNRNPA2/B1 | HNRNPA2B1 ↑ → pri-miR-106b ↓, pre-miR-106b ↑, miR-106b-5p ↑ → SFRP2 ↓ → activates Wnt/β-catenin signaling | Promotes cell stemness, proliferation, migration and tumor growth of lung adenocarcinoma cells | Lung cancer | [77] |
miR-663 | METTL3 | METTL3 ↑ → m6A-modified pri-miR-663 ↑ → pri-miR-663 ↓, miR-663 ↑ → SOCS6 ↓ | Promotes proliferation, migration and invasion of lung cancer cells | Lung cancer | [78] |
miR-486 | Unknown | Propofol treatment → m6A-modified pri-miR-486 ↑ → pri-miR-486 ↓, miR-486-5p ↑ → inactivates the RAP1-NF-kappaB signaling axis | Enhances cisplatin-sensitivity | Lung cancer | [79] |
miR-576 | FTO | FTO ↑ → m6A -modified pri-miR-576 ↓ → pri-miR-576 ↑, miR-576 ↓ → CDK6 ↑ | Promotes tumor proliferation and invasion | Bladder cancer | [80] |
miR221/222 | METTL3 | METTL3 ↑ → m6A-modified pri-miR221/222 ↑ → pri-miR221/222 ↓, miR221/222 ↑ → PTEN ↓ | Promotes tumor proliferation | Bladder cancer | [81] |
miR-146 | METTL3 | Melittin stimulation → METTL3 ↓ → m6A-modified pri-miR-146 ↓ → pri-miR-146 ↑, miR-146a-5p ↓ → regulates NUMB/NOTCH2 pathway | Induces apoptosis and inhibits tumor growth | Bladder cancer | [82] |
miR-125b2 | NSun2 | PAR2 activation → m6A-modified pre-miR-125b2 in a Nsun2-dependent manner ↑ → miR-125b2 ↓ → Gab2 ↑ | Promotes cancer cell migration | Colorectal cancer, lung cancer | [65] |
miR-126 | METTL14 | METTL14 ↓ → m6A-modified pri-miR-126 ↓ → pri-miR-126 ↑, miR-126 ↓ | Enhances cell metastasis | Liver cancer | [83] |
miR‐589-5p | METTL3 | METTL3 ↑ → m6A-modified pri‐miR‐589 ↑ → pri-miR-589 ↓, miR‐589‐5p ↑ | Promotes cell viability, migration and invasion | Liver cancer | [84] |
miR-194–2 and miR-532 | ALKBH5 | ALKBH5 ↑ → m6A-modified pri-miR-194 ↓ → miR-194–2 ↓ → RAI1 ↑ → regulates the Hippo pathway | Inhibits cell growth and motility | Esophageal cancer | [85] |
miR-99a | METTL14 | METTL14 ↓ → m6A-modified pri-miR-99a ↑ → miR-99a ↑ → TRIB2 ↓ | Promotes cancer stem cell persistence and radioresistance | Esophageal cancer | [86] |
miR-92b | METTL3 | Deoxycholic acid treatment → METTL3 dissociation from METTL14 and WTAP complex → m6A-modified pri-miR-92b ↓ → miR-92b ↓ → PTEN ↑ → activates PI3K/AKT signaling | Enhances cell proliferation | Gallbladder cancer | [87] |
miR-19a | METTL3 | METTL3 ↑ → m6A-modified pri-miR-19a ↑ → miR-19a ↑ → BAMBI ↓ | Facilitates nasopharyngeal carcinoma cell proliferation and invasion | Nasopharyngeal carcinoma | [88] |
miR-126-5p | METTL3 | METTL3 ↑ → m6A-modified pri-miR-126-5p ↑ → miR-126-5p ↑ → PTEN ↓ activates PI3K/Akt/mTOR pathway | Promotes cell proliferation, migration and invasion and inhibits apoptosis | Ovarian cancer | [89] |
miR-1246 | METTL3 | METTL3 ↑ → pri-miR-1246 ↓, miR-1246 ↑ → CCNG2 ↓ | Promotes the proliferation and metastasis and inhibits apoptosis | Ovarian cancer | [90] |
miR-25-3p | METTL3 | Cigarette smoke stimulation → METTL3 ↑, with NKAP as a reader → m6A-modified pri-miR-25 ↑ → pri-miR-25↓, pre-miR-25 ↑, miR-25-3p ↑ | Promotes pancreatic cancer cell proliferation, migration and invasion | Pancreatic cancer | [91] |
miR-30d | YTHDC1 | YTHDC1 ↓ → pri-miR-30d ↑ → miR-30d ↓ → RUNX1 ↑ → SLC2A1 ↑, HK1 ↑ | Promotes aerobic glycolysis to potentiate tumor proliferation, metastasis and angiogenesis | Pancreatic cancer | [92] |
miR-222-3p | METTL3 | METTL3 ↑ → m6A-modified pri-miR-222-3p ↑ → miR-222-3p ↑ → STK4 ↓ | Promotes tumor growth and metastasis | Thyroid carcinoma | [93] |
miR-143-3p | KIAA1429 and ALKBH5 | KIAA1429 ↓, ALKBH5 ↑ → m6A-modified pri-miR-143-3p ↓ → pri-miR-143-3p ↑, miR-143-3p ↓ → DDX6 ↑ | Suppresses human aortic smooth muscle cell proliferation, promotes human aortic endothelial cell apoptosis and facilitates aortic dissection progression | Aortic dissection | [94] |
miR-19a | METTL14 | METTL14 ↑ → m6A-modified pri-miR-19a ↑ → miR-19a ↑ | Promotes cardiovascular endothelial cell proliferation and invasion | Atherosclerosis | [95] |
miR-25-3p | METTL3 | METTL3 ↓ → miR-25-3p ↓ → PTEN ↑ → phosphorylated Akt ↓ | Attenuates high-glucose induced retinal pigment epithelium cell pyroptosis | Diabetic retinopathy | [96] |
miR-93 | METTL3 | Cigarette smoke stimulation → METTL3 ↑→ m6A-modified pri-miR-93 ↑ → pri-miR-93 ↓, pre-miR-93 ↑, miR-93 ↑ → miR-93 endocytosed from bronchial epithelial cells into macrophages through extracellular vesicle trafficking ↑ → DUSP2 ↓ → MMP9 ↑, MMP12 ↑, activates JNK pathway | Induces elastin degradation | Emphysema | [97] |
miR-126 | METTL3 | METTL3 ↓ → m6A-modified pri-miR126 ↓ → pri-miR126 ↑, miR126 ↓ | Facilitates the migration and invasion of human endometrial stromal cells | Endometriosis | [98] |
miR-365-3p | METTL3 | METTL3 ↑ → m6A-modified pri-miR-365-3p ↑ → pri-miR-365-3p ↓, miR-365-3p ↑ | Produces pain-related behaviors and neuronal sensitization in naive mice | Inflammatory pain | [99] |
miR-34-5p | METTL14 | METTL14↑ → pri-miR-34 ↓, pre-miR-34 ↑, miR-34a-5p ↑ → SIRT1↓ | Promotes cell cycle arrest and senescence | Intervertebral disc degeneration | [100] |
miR-221/222 | METTL3 | Angiotensin II stimulation → METTL3 ↑ → m6A-modified pri-miR-221/222 ↑→ miR-221/222 ↑ → DKK2 ↓ → activates Wnt/β-catenin signaling | Promotes Ang-II-induced cardiac hypertrophy | Myocardial hypertrophy | [101] |
miR-143 | METTL3 | METTL3 ↓ → m6A-modified pri-miR-143 ↓ → pri-miR-143↑, pre-miR-143 ↑, miR-143 ↓ → Yap ↑, Ctnnd1 ↑ | Promotes cardiomyocyte proliferation and endogenous cardiac repair after myocardial infarction | Myocardial infarction | [102] |
miR-17-3p | METTL3 | METTL3 ↑ → increases binding between DGCR8 and pri-miR-17-3p → miR-17-3p ↑ | Ameliorates hypoxia-induced decrease in myoproliferative capacity and increase in apoptosis | Myocardial infarction | [103] |
miR-150 | METTL3 | METTL3 ↓, with YTHDF2 as a reader → m6A-modified pri-miR-150 ↓ → miR-150 ↓ → BDNF ↓ | Increases the severity of neuropathic pain | Neuropathic pain | [104] |
miR‐21 | METTL3 | METTL3 ↑, with HNRNPA2B1 as a reader → m6A-modified pri‐miR‐21 ↑ → miR‐21‐5p ↑ → activates the SPRY1/ERK/NF‐kB signaling pathway | Promotes inflammation and the development of obstructive renal fibrosis | Obstructive renal fibrosis | [105] |
miR-320a-3p | ALKBH5 | ALKBH5 ↑ → m6A-modified pri-miR-320a-3p ↓ → pri-miR-320a-3p ↑, miR-320a-3p ↓ → FOXM1↑ | Promotes lung fibroblast activation and silica-induced pulmonary fibrosis | Silica-induced pulmonary fibrosis | [61] |
miR-335 | METTL3 | METTL ↑ → m6A-modified pri-miR-335 ↑ → pri-miR-335 ↓, pre-miR-335 ↑, miR-335 ↑→ Erf1 ↓ | Promotes stress granule formation and reduces the level of apoptosis in neurons and other cells | Acute ischemic stroke | [106] |