Table 3 Important enzymes or proteins that regulate histone methylation in cancer.

 KMT1A

SUV39H1, MG44, SUV39H

Promoter

Gastric cancer, prostate cancer, breast cancer, lung cancer, colorectal cancer, bladder cancer^{421,422,423,424,425,426}

Promotes cell migration and cancer stem cell self-renewal (KMT1A-GATA3-STAT3 axis)

Suppressor

Breast cancer, cervical cancer^427,428

SUV39H1-low tumors are correlated with poor clinical outcomes

 KMT1B

FLJ23414, SUV39H2

Promoter

Colorectal cancer, lung cancer, gastric cancer^429,430,431

Promotes cell proliferation, migration and invasion and tumor metastasis

 KMT1C

EHMT2, G9A, BAT8, NG36

Promoter

Breast cancer, pancreatic cancer, bladder cancer, ovarian cancer, liver cancer, colon cancer, lung cancer^{432,433,434,435}

Promotes cell proliferation, metastasis, and apoptosis, and is associated with poor prognosis (p27, PMAIP1-USP9X-MCL1 axis, Wnt signaling pathway)

 KMT1E

SETDB1, ESET, KG1T

Promoter

Breast cancer, colorectal cancer, hepatocellular carcinoma, liver cancer^{436,437,438,439}

SETDB1 promotes cell proliferation, migration, invasion, and EMT (p53)

Suppressor

Lung cancer⁴⁴⁰

SETDB1 acts as a metastasis suppressor, and inhibits cell migration and invasive behavior.

 KMT2A

MLL1, HRX, TRX1, ALL-1

Promoter

Head and neck cancer, pancreatic cancer, prostate cancer^441,442

Promotes PD-L1 transcription and is associated with the self-renewal of cancer cells (Wnt/β-catenin pathway)

 KMT2B

ALR, MLL2

promoter

Bladder cancer, lung cancer, breast cancer^443,444,445

Is associated with the self-renewal of CSCs and expansion (Wnt/β-catenin pathway)

 KMT2C

MLL3, HALR

Suppressor

Colorectal cancer, esophageal squamous cell carcinoma⁴⁴⁶

Inhibits tumor growth and metastasis

 KMT2D

MLL4, HRX2

Promoter

Breast cancer⁴⁴⁷

Promotes cell proliferation and invasiveness

 KMT2E

MLL5

Promoter

Glioblastoma⁴⁴⁸

Is associated with cancer cell self-renewal

 KMT2F

SET1A

Promoter

Liver cancer⁴⁴⁹

Promotes liver cancer growth and hepatocyte-like stem cell malignant transformation

 EZH1

KIAA0388

Promoter

Breast cancer, prostate cancer, bladder cancer, colorectal cancer, liver cancer, gastric cancer, melanoma, lymphoma, myeloma, Ewing’s sarcoma, glioblastoma, thyroid carcinoma, esophageal squamous cell carcinoma, lung cancer, ovarian cancer, renal cancer^{392,450,451,452}

Promotes cell proliferation, colony formation, migration and tumor metastasis; is associated with cancer stem cell maintenance; predicts chemotherapeutic efficacy and response to tamoxifen therapy (E-cadherin, RUNX3, MEK-ERK1/2-Elk-1 pathway)

 EZH2

KMT6, ENX-1, MGC9169

 KMT3A

SETD2, SET2, HIF-1,

Suppressor

Renal cancer, lung cancer^453,454

Maintains genome integrity and attenuates cisplatin resistance (ERK signaling pathway)

 WHSC1

NSD2, WHS, TRX5

Promoter

Prostate cancer, gastric cancer^455,456

Promotes cell invasive properties, EMT and cancer metastasis

 WHSC1L1

NSD3, MGC126766

Promoter

Breast cancer, head and neck cancer⁴⁵⁷

Is associated with ERα overexpression and enhances the oncogenic activity of EGFR

 PRDM1

BLIMP1

Promoter

Pancreatic cancer, breast cancer^458,459

Promotes cell invasiveness and cancer metastasis

Suppressor

Lung cancer, colon cancer^460,461

Inhibits cell invasion and metastasis (p21)

 PRDM2

RIZ

Promoter

Colorectal cancer, breast cancer^462,463

Is associated with poor clinicopathological variables and mediates the proliferative effect of estrogen

 PRDM3

EVI1, MDS1-EVI1

Promoter

Ovarian cancer, nasopharyngeal carcinoma^464,465

Promotes cell proliferation, migration, EMT, cancer stem cells and chemoresistance/radioresistance

 PRDM4

PFM1

Promoter

Breast cancer⁴⁶⁶

Is associated with cancer cell stemness, tumorigenicity, and tumor metastasis

 PRDM5

PFM2

Suppressor

Colorectal cancer, gastric cancer, cervical cancer⁴⁶⁷

Among the PRDM family genes tested, PRDM5 was the most frequently silenced in colorectal and gastric cancer

 PRDM9

PFM6

Promoter

N/A⁴⁶⁸

Impairs genomic instability and drives tumorigenesis

 PRDM14

PFM11

Promoter

Testicular cancer, pancreatic cancer^469,470

Is associated with early germ cell specification and promotes cancer stem-like properties and liver metastasis

 PRDM16

MEL1, PFM13

promoter

Gastric cancer⁴⁷¹

Inhibits TGF-beta signaling by stabilizing the inactive Smad3-SKI complex

 KMT3C

SMYD2

Promoter

Pancreatic cancer, gastric cancer, breast cancer, lung cancer^472,473

Promotes cancer cell proliferation and survival (STAT3, EML4-ALK, p65)

 KMT3E

SMYD3, ZMYND1, ZNFN3A1, FLJ21080

Promoter

Liver and colon cancer, prostate cancer, breast cancer^474,475,476

Promotes cell proliferation, invasion, EMT and cancer stem cell maintenance (Myc, MMP-9, Ctnnb1, JAK/Stat3 pathway, Wnt pathway, androgen receptor transcription)

 SMYD4

ZMYND21

Suppressor

Breast cancer⁴⁷⁷

SMYD4 acts as a suppressor in tumorigenesis

 DOT1L

KMT4

promoter

MLL-rearranged leukemia, colorectal cancer, breast cancer, ovarian cancer^391,478,479

Increases EMT, cancer stemness and tumorigenic potential and is required for MLL rearrangement

 SET8

KMT5A, SETD8, PR-set7

promoter

Breast cancer, prostate cancer, ovarian cancer, lung cancer^480,481

Promotes cell proliferation, migration, invasion, and EMT (MiR-502)

 SUV4-20H2

KMT5C, MGC2705

Suppressor

Breast cancer⁴⁸²

SUV4-20H2 is downregulated in breast cancer

 SetD6

/

Promoter

Colorectal cancer, bladder cancer, breast cancer^483,484

Promotes cell survival and colony formation and contributes to increased susceptibility to cancer

 SET7/9

SETD7, KMT7

Suppressor

Breast cancer, gastric cancer, AML, lung cancer^485,486,487

Promotes cell proliferation, EMT and the generation of cancer stem cells; a low level of SET7/9 is correlated with clinical aggressiveness and worse prognosis (β-catenin stability)

 PRMT1

ANM1, HCP1, IR1B4

Promoter

Breast cancer, colon cancer, gastric cancer, lung cancer^488,489,490

Promotes EMT, cancer cell migration, and invasion and is associated with chemosensitivity and poor clinical and histological parameters

Suppressor

Pancreatic cancer⁴⁹¹

Inhibits cell proliferation and invasion in pancreatic cancer

 PRMT2

/

Suppressor

Breast cancer⁴⁹²

Induces cell cycle arrest and apoptosis in breast cancer

 PRMT4

CARM1

Promoter

Ovarian cancer, breast cancer, liver cancer, colorectal cancer, prostate cancer^450,493,494

Promotes cell proliferation and blocks cell differentiation (Wnt/β-catenin signaling)

Suppressor

Pancreatic cancer⁴⁹⁵

Inhibits glutamine metabolism and suppresses cancer progression

 PRMT5

JBP1, SKB1, IBP72

Promoter

Breast cancer, prostate cancer, colorectal cancer, lung cancer^496,497,498

Promotes cell survival, proliferation, invasiveness and sensitivity to 5-Fluorouracil (5-FU) (SHARPIN-PRMT5-H3R2me1 axis)

Suppressor

Breast cancer⁴⁹⁹

High PRMT5 expression favors a better prognosis in BC patients

 PRMT6

HRMT1L6

Promoter

Prostate cancer, gastric cancer^500,501

Is associated with cell apoptosis, invasiveness and viability (PI3K/AKT/mTOR pathway, H3R2me2as)

Suppressor

Hepatocellular carcinoma⁵⁰²

Negatively correlates with aggressive cancer features

 PRMT7

FLJ10640, KIAA1933

Promoter

Lung cancer, breast cancer^503,504

Promotes cancer cell EMT and tumor metastasis

 PRMT8

HRMT1L3, HRMT1L4

Promoter

Breast, ovarian and gastric cancer⁵⁰⁵

Overexpression of PRMT8 is correlated with decreased patient survival

 PRMT9

FBXO11

Promoter

Breast cancer⁵⁰⁶

Fuels tumor formation via restraint of the p53/p21 pathway

 HP1

/

Promoter

Breast cancer⁵⁰⁷

Overexpression of HP1 is associated with breast cancer progression

 Chd1

/

Promoter

Prostate cancer⁵⁰⁸

Is associated with cell invasiveness, double-strand break repair and response to DNA-damaging therapy

Suppressor

Prostate cancer⁵⁰⁹

Loss of MAP3K7 and CHD1 promotes an aggressive phenotype in prostate cancer

 WDR5

/

/

/

 BPTF

/

Promoter

Lung cancer, hepatocellular carcinoma^510,511

Promotes cell proliferation, migration, stem cell-like traits and invasion (miR-3666)

 L3MBTL1

/

Suppressor

Breast cancer⁵¹²

Expression of L3MBTL1 is associated with a low risk of disease recurrence and breast cancer-related death

 ING2

Promoter

Colon cancer⁵¹³

Increases invasion by enhancing MMP13 expression

Suppressor

Lung cancer⁵¹⁴

Suppresses tumor progression via regulation of p53

BHC80

Promoter

Prostate cancer⁵¹⁵

Stimulates cell proliferation and tumor progression via the MyD88-p38-TTP pathway

JMJD2A

Promoter

Breast cancer, liver cancer, colon cancer^516,517

Promotes cells apoptosis and proliferation and contributes to tumor progression (ARHI, miR372)

Suppressor

Bladder cancer⁵¹⁸

Low JMJD2A correlates with poor prognostic features and predicts significantly decreased overall survival

 KDM1A

LSD1

Promoter

Breast cancer, lung cancer, prostate cancer, liver cancer, pancreatic cancer, gastric cancer^519,520,521

Contributes to cell proliferation and stem cell maintenance and self-renewal (p21, AR, HIF1α-dependent glycolytic process)

Suppressor

Breast cancer⁵²²

Inhibits invasion and metastatic potential

 KDM1B

LSD2

Promoter

Breast cancer⁵²³

Contributes to cancer progression and cancer stem cell enrichment

 KDM2A

JHDM1A, CXXC8

Promoter

Breast cancer, gastric cancer, lung cancer, cervical cancer^524,525,526

Promotes cancer cell proliferation, metastasis, and invasiveness (HDAC3, TET2)

 KDM2B

JHDM1B, FBXL10,

Promoter

Prostate cancer, breast cancer, gastric cancer^527,528

Promotes cell migration, angiogenesis, and the self-renewal of cancer stem cells

 KDM3A

JHDM2A, JMJD1A

Promoter

Colorectal cancer, ovarian cancer, breast cancer, prostate cancer, bladder cancer^529,530,531

Promotes cancer cell growth, metastasis, stemness and chemoresistance (c-Myc, Wnt/β-catenin signaling, glycolysis, HIF1α)

 KDM3C

JHDM2C, JMJD1C

Promoter

Esophageal cancer, colorectal cancer^532,533

Promotes cancer cell proliferation and metastasis (YAP1 signaling, ATF-2)

 KDM4A

JHDM3A, JMJD2A

Promoter

Breast cancer, liver cancer^516,534

Promotes cancer progression through repression of the tumor suppressor ARHI (miR372)

Suppressor

Bladder cancer⁵¹⁸

Downregulated in cancer tissues and significantly decreases as cancer progresses

 KDM4B

JMJD2B

Promoter

Breast cancer, gastric cancer, ovarian cancer, colorectal cancer, prostate cancer^535,536,537

Promotes EMT and metastasis, and regulates the seeding and growth of peritoneal tumors; is involved in resistance to PI3K inhibition (p-ERK, β-catenin)

 KDM4C

JMJD2C, GASC1

Promoter

Breast cancer, pancreatic cancer^538,539

Promotes cancer progression (HIF-1α, miR-335-5p)

 KMD4D

JMJD2D

Promoter

Colorectal cancer⁵⁴⁰

Promotes cell proliferation and tumor growth (β-catenin)

 KDM5A

JARID1A, RBP2

Promoter

Breast cancer, colorectal cancer, cervical cancer^541,542

Promotes proliferative activity and invasion, and inhibition of KDM5A causes growth arrest at the G1 phase (c-Myc)

 KDM5B

JARID1B, RBP2-like

Promoter

Colorectal cancer, lung cancer, gastric cancer⁵⁴³

Promotes cell proliferation, metastasis, and expression of CSCs, and inhibition of KDM5B results in cell cycle arrest, apoptosis, and senescence (E2F/RB pathway)

 KDM5C

JARID1C, SMCX

Promoter

Prostate cancer, lung cancer⁵⁴⁴

Overexpression of KDM5C predicts therapy failure and is associated with cancer cell growth, migration and invasion

Suppressor

Colon cancer⁵⁴⁵

Inhibits the multidrug resistance of colon cancer cell lines by downregulating ABCC1

 KDM5D

JARID1D, SMCY

Promoter

Gastric cancer⁵⁴⁶

Promotes cell proliferation and EMT

Suppressor

Prostate cancer⁵⁴⁷

Loss of KDM5D expression induces resistance to docetaxel

 JARID2

JUMONJI

Promoter

Bladder cancer, lung and colon cancers^548,549

Regulates cancer cell EMT and stem cell maintenance and is associated with poor survival

Suppressor

Prostate cancer⁵⁵⁰

Inhibits cell proliferation, migration, and tumor development via inhibition of Axl

 KDM6A

UTX

Promoter

Breast cancer⁴⁴⁷

Promotes cell proliferation and invasiveness

Suppressor

Bladder cancer, pancreatic cancer^551,552

KDM6A loss induces squamous-like, metastatic pancreatic cancer

 KDM6B

JMJD3

Promoter

Ovarian cancer, breast cancer, gastric cancer^553,554

High expression of KDM6B is correlated with poor prognosis

 KDM6C

UTY

Suppressor

Bladder cancer⁵⁵⁵

UTY-knockout cells have increased cell proliferation compared to wild-type cells

 KDM7A

JHDM1D

Promoter

Prostate cancer⁵⁵⁶

Promotes cell proliferation and upregulated androgen receptor activity

 KDM7C

PHF2, JHDM1E

Suppressor

N/A⁴²⁰

Is a suppressor and promotes p53-driven gene expression

 KDM7B

PHF8, JHDM1F

Promoter

Prostate cancer, gastric cancer, lung cancer, leukemia, colorectal cancer^557,558,559

Promotes cell proliferation, migration and invasion, and high PHF8 expression predicts poor survival (miR-488)

 JMJD5

KDM8

Promoter

Breast cancer^560,561

Promotes metastasis and indicates a poor prognosis; is required for cell cycle progression via because of its actions in the cyclin A1 coding region.

 RSBN1

KDM9

Promoter

Breast cancer⁵⁶²

Is a new potential HIF target

 JMJD6

PSR, PTDSR

Promoter

Breast cancer, oral cancer, lung cancer^563,564,565

Promotes cancer cell proliferation, EMT and motility, and maintains cancer cell stemness properties (autophagy pathway, WNT/β-catenin pathway)

 PADI4

/

Promoter

Breast cancer, esophageal cancer⁵⁶⁶

Promotes cancer progression and is correlated with pathological classification (c-Fos)