Table 2 Summary of m6A modifications to small RNAs and their cellular functions in homeostasis and human disease

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]