Table 2.
The roles of PRMTs in cancer.
| PRMTs | Cancer type | Expression | Function | Biological mechanism | Ref. |
|---|---|---|---|---|---|
| PRMT1 | |||||
| Breast cancer | High | Oncogenic | Activation of IGF-1 signaling by ERα methylation in breast cancer | 207 | |
| EZH2 methylation (R342) leading to an increase in EMT | 65 | ||||
| C/EBPα methylation (R35/156/165) leading to activation of Cyclin D1 expression | 156 | ||||
| Activation of ZEB1 transcription leading to cell growth and metastasis | 208 | ||||
| Pancreatic cancer | High | Oncogenic | Enhancement of oncogenic GLI1 function by R597 methylation | 67 | |
| HSP70 methylation leading to stabilization of BCL2 mRNA | 209 | ||||
| Colorectal cancer | High | Oncogenic | Activation of EGFR signaling through EGFR methylation (R198/200) | 66 | |
| Lung | High | Oncogenic | Regulation of the EMT through Twist1 methylation (Arg34) | 68 | |
| HCC | High | Oncogenic | Downregulation of CDKN1A | 210 | |
| Melanoma | High | Oncogenic | Increase in ALCAM expression leading to tumor growth and metastasis | 211 | |
| Head and neck cancer | High | Oncogenic | Increase of growth rate, reduction in migration activity, and increase in E-cadherin expression | 212 | |
| ESCC | High | Oncogenic | Activation of Hedgehog signaling leading to tumor growth, migration, and metastasis | 213 | |
| PRMT2 | |||||
| Breast cancer | High | Oncogenic | Three spliced variants of PRMT2 are overexpressed in breast cancer; they bind to and activates ERα | 214 | |
| Low | Tumor suppressive | Downregulates Cyclin D1 expression | 69 | ||
| Glioblastoma | High | Oncogenic | Transcriptional activation of oncogenes via H3R8me2a | 70 | |
| PRMT3 | |||||
| Pancreatic cancer | High | Oncogenic | Activation of GAPDH by methylation (R248) and enhancement of glycolysis in cancer | 215 | |
| CARM1 | |||||
| Breast cancer | High | Oncogenic | Upregulation of Cyclin E1 leading to the promotion of S-phase entry | 34 | |
| Enhancement of tumor progression and metastasis through BAF155 methylation (R1064) | 71 | ||||
| Stabilization of LSD1 protein by methylation (R838) | 216 | ||||
| — | Tumor suppressive | Inhibition of cell proliferation and induction of differentiation in breast cancer | 74 | ||
| Sensitization to chemotherapy drugs through MED12 methylation (R1862/1912) | 75 | ||||
| Colorectal cancer | High | Oncogenic | Activation of Wnt/β-catenin transcription and cancer cell growth | 217 | |
| Pancreatic cancer | Low | Tumor suppressive | Suppression of cell growth and glutamine metabolism through MDH1 methylation (R248) | 218 | |
| HCC | Low | Tumor suppressive | Inhibition of GAPDH1 by arginine methylation (R234) leading to facilitation of glycolysis in liver cancer cells | 219 | |
| Ovarian cancer | high | Oncogenic | Promotion of EZH2-mediated silencing of EZH2/BAF155 target tumor suppressor genes | 220 | |
| AML | high | Oncogenic | Methylation of RUNX1 (R223) by CARM1 blocks myeloid differentiation | 221 | |
| Facilitation of myeloid leukemogenesis | 222 | ||||
| PRMT5 | |||||
| Lymphoma | High | Oncogenic | Activation of WNT/β-catenin and AKT/GSK3β signaling in lymphoma | 223 | |
| Leukemia/lymphoma | High | Oncogenic | Suppression of the transcription of RB family | 224 | |
| DLBCL | High | Oncogenic | PRMT5 upregulation by BCR-BKT-NF-κB signaling | 93 | |
| AML | — | Oncogenic | Regulation of alternative splicing through SRSF1 methylation | 225 | |
| — | Oncogenic | Silencing of miR-29b and an increase in SP1 and FLT3 expression | 94 | ||
| Breast cancer | High | Oncogenic | Regulation of alternative splicing through ZNF326 methylation (R175) | 188 | |
| Increase in resistance to chemotherapeutics by regulating stemness-related genes such as OCT4/A, KLF4, and C-Myc | 226 | ||||
| Promotion of cell proliferation through interaction with TRAF4 in the nucleus | 227 | ||||
| Essential for breast cancer stemness via the activation of FOXP1 transcription | 79 | ||||
| Lung cancer | High | Oncogenic | Repression of miR-99 family transcription and activation of FGFR3/ERK/AKT pathway | 99 | |
| Promotion of lung cancer cell proliferation through direct interaction with and activation of AKT | 228 | ||||
| PRMT5-SHARPIN complex-mediated H3R2me1 activates transcription of metastasis-related genes | 229 | ||||
| PRMT5-mediated Enolase-1 methylation (R50me1) enhances localization to the surface membrane | 230 | ||||
| Prostate cancer | High | Oncogenic | Activation of AR transcription via H4R3me2s with pICln coactivator | 98 | |
| Methylation of AR (R761), leading to attenuation of AR-mediated transcription involved in differentiation | 231 | ||||
| Gastric cancer | High | Oncogenic | PRMT5 expression positively correlates with the expression of GENMIN2, STAT3, and TGFB3, and malignant phenotype | 86 | |
| Direct interaction with c-Myc to suppress the transcription of PTEN, CDKN2C, CDKN1A, CDKN1C, and p63 | 232 | ||||
| PRMT5-mediated histone methylation recruits DNMT3A to silence IRX1 | 85 | ||||
| HCC | High | Oncogenic | Enhancement of invasive activity via regulation of MMP-2 expression | 87 | |
| Promotion of HCC proliferation by downregulating BTG2 expression | 88 | ||||
| Pancreatic cancer | high | Oncogenic | Downregulation of FBW7 leading to stabilization of c-Myc | 89 | |
| Activation of EGFR-AKT-GSK3β-β-catenin signaling leading to cell growth | 90 | ||||
| Colorectal cancer | High | Oncogenic | Methylation YBX1 (R205) is essential for NF-κB activation and CRC growth and migration | 84 | |
| Melanoma | High | Oncogenic | SHARPIN facilitates PRMT5 activity that increases SOX10 and PAX3 expression | 95 | |
| Regulation of MDM4 expression via alternative splicing, which results in resistance to the CDK4/6 inhibitor | 233 | ||||
| Glioblastoma | High | Oncogenic | Silencing of the ST7 tumor suppressor gene leading to tumor cell growth and survival | 96 | |
| Bladder cancer | High | Oncogenic | Enhancement of NF-κB activation, thereby increasing BCL-XL/cIAP1 | 92 | |
| MTAP deleted cancer | Increased endogenous MTA inhibits PRMT5 activity and induces vulnerability toward PRMT5 | 101–103 | |||
| PRMT6 | |||||
| Gastric cancer | High | Oncogenic | Enhances global H3R2me2a and suppresses several tumor suppressor genes including PCDH7, SCD, and IGFBP5 | 234 | |
| Endometrial cancer | High | Oncogenic | Facilitation of EMC cell proliferation and migration via the activation of AKT/mTOR signaling | 235 | |
| Lung cancer | High | Oncogenic | Activation of tumor-associated macrophages via interaction with ILF2 | 236 | |
| HCC | Low | Tumor suppressive | Methylation of CRAF (R100) by PRMT6 inhibits RAS/RAF binding and MEK-ERK signaling | 202 | |
| PRMT7 | |||||
| Breast cancer | High | Oncogenic | Increase in MMP9 expression | 237 | |
| Promotion of metastasis through SHANK2 methylation (R240)-mediated FAK activation | 106 | ||||
| Lung (NSCLC) | High | Oncogenic | Promotion of the invasion and colony formation through interaction with HSPA5 and EEF2 | 238 | |
| Renal cell carcinoma | High | Oncogenic | Upregulation of c-Myc expression via β-catenin methylation | 239 | |
| PRMT9 | |||||
| HCC | High | Oncogenic | Promotion of invasion and metastasis through PI3K/AKT/GSK3β/Snail signaling activation | 240 | |
HCC hepatocarcinoma, ESCC esophageal squamous-cell carcinoma, AML acute myeloid leukemia, DLBCL diffuse large B-cell lymphoma, MTAP methylthioadenosine phosphorylase, NSCLC non-small cell lung carcinoma.