The Role and Mechanism of the Histone Methyltransferase G9a in Tumors: Update

Figures & data

Table 1 The Pathways and Function of G9a in Various System Tumors

Tumor Type	Pathway	Function
MB	G9a/TP53	Poor prognosis^Citation19,Citation20
GBM	G9a-PARP3/Nfasc, Parvb, MLH1, Hif-2α, RUNX3, Ndrg1, Ndrg2, Ndrg4	Invasion^Citation21
Gliomas	G9a/MHC-I, Fbxw7	Poor prognosis^Citation22
NSCLC	G9a/NF-Κb/FAK	Invasion and metastasis^Citation23
LUAD	AT2/G9a	Proliferation^Citation24
	CNB/G9a, FOXO1	Regulating the proliferation, migration, and invasion of A549 cells and their apoptosis^Citation25
	G9a/CCDC8	Radiation resistance^Citation26
	ROS/Snail/G9a	EMT^Citation27
	G9a/NFYA/ALDH2	Mediation of resistance to Paclitaxel in vitro and in vivo^Citation28
EC	LSD1-G9a/ER stress pathway	Poor prognosis^Citation29
GC	Hypoxia/G9a/RUNX3	Proliferation^Citation30
	G9a/CA	Cellular autophagy^Citation31
	SPINK1	Not yet clear^Citation32
	CALR/G9a/E-cadherin	Promote the migration of GC cells in vitro and in vivo^Citation33
HCC	G9a/miR-122	Poor prognosis^Citation34
	DNA damage/G9a/Bcl-G-p53	Occurrence of tumors^Citation35
	G9a/SLC7A2/PI3K/Akt/NF-kκB/CXCL1	Inhibition metastasis^Citation36
	G9a/MMP2, MMP9, CD44v6, VEGF	Not yet clear^Citation37
	CDK9/G9a/MYC	Cancer growth and invasive^Citation38
HB	G9a/DNMT1/UHRF1	Cancer development^Citation39
CCA	G9a/ (MYC/Max heterodimer) / 15-PGDH	Promote CCA cell growth^Citation40
iCCA	KRASG12D/G9a/PHGDH	Increasing iCCA cell viability^Citation41
PDAC	Tetraspanin1/FAM110A/ HIST1H2BK /G9a	Cancer progression^Citation42
CRC	Not yet clear	Driving cancer stem cell phenotype^Citation43,Citation44
	G9a/ZNF518B/ RGS4, PADI3	Metastasis^Citation45
	G9a/IL8	Suppress cancer stemness and enhance chemosensitivity^Citation46,Citation47
	Butyrate/ HECTD2/G9a	Promote CRC growth^Citation48
BCa	MYC/G9a/FTH1	Promote occurrence and progression of cancer^Citation49–51
	G9a/BMP5/Smad	Regulate the growth and metastasis of BCa cells^Citation52
TNBC	Low-glucose/G9a	Invasion and migration^Citation53
HGSC	G9a and EZH2/CXCL10/CXCR3	Altering the immune microenvironment and tumor growth^Citation54
PCa	PALI1/G9a/PRC2	Poor prognosis^Citation55
	Paclitaxel/SPOP/G9a	Promote PCa cell growth^Citation56
	G9a/ERP29	Radioresistance^Citation57
RCC	G9a/ /p53	Carcinogenic effects^Citation58
AML	Destabilization of the complex composed of SUV39H1, GLP and G9a/IFN	Proliferation^Citation59
	Not yet clear	Drug resistance and relapse^Citation60
ALL	G9a/lysosome biogenesis/SESN2/GSK-3	Impairs glycogen metabolism^Citation61
CML	G9a/SOX6	Reduce self-renewal in CML^Citation62
MM	G9a, GLP/Mtor/ EIF4EBP1 /MYC/p38/MAPK9/JNK	Worse disease outcomes in newly diagnosed and relapsed^Citation63
	EZH2, G9a/IFN-stimulated genes/IRF4/MYC	Inhibiting cell growth^Citation64
MCL	Not yet clear	Cell cycle^Citation65
PTC	TESC/ALDH1A1/βIII-tubulin/PTEN	Promote tumor growth^Citation66
ARMS	NR4A1/G9a	Not yet clear^Citation67
	DDX5/G9a/AKT	Tumor growth^Citation68
	H3F3A/G9a/MCAM	Potential therapeutic target^Citation69
EWS	G9a/NEU1	Impairing in vitro and in vivo metastasis^Citation70
HNSCC	BRD4/G9a/MHC-I	Inhibiting anti-tumor immunity^Citation71
OSCC	G9a/SPINK5/Wnt pathway	Invasion^Citation72

Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ARMS, alveolar rhabdomyosarcoma; BCa, breast cancer; CCA, cholangiocarcinoma; CML, chronic myeloid leukemia; CRC, colorectal cancer; EC, esophageal cancer; EWS, ewing sarcoma. GBM, glioblastoma; GC, gastric cancer; HB, hepatoblastoma; HCC, hepatocellular carcinoma; HGSC, high-grade serous ovarian carcinoma; HNSCC, head and neck squamous cell carcinoma; iCCA, thioacetamide-induced intrahepatic CCA; LUAD, lung adenocarcinoma; MB, medulloblastoma; MCL, mantle cell lymphoma; MM, multiple myeloma; NSCLC, non-small cell lung cancer; OSCC, oral squamous cell carcinoma; PCa, prostate cancer; PDAC, pancreatic ductal adenocarcinoma; PTC, papillary thyroid carcinoma; RCC, renal cell carcinoma; TNBC, triple-negative BCa.

Figure 1 The role and pathways of G9a in various systemic tumors.

Figure 2 (A) The gene expression profile across all tumor samples and paired normal tissues (Dot plot), each dots represent expression of samples. (B) The gene expression profile across all tumor samples and paired normal tissues (Bar plot), the height of bar represents the median expression of certain tumor type or normal tissue. (C) Disease free survival rate of G9a in tumors. (D) Overall survival rate of G9a in tumors. Tang Z. et al (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res, 10.1093/nar/gkx247.⁷⁹

Table 2 The Cancer Type and Function of G9a Inhibitor in Various System Tumors

Inhibitor	Cancer	Function
CM-272	MM	Reversing MM-associated bone disease
	HCC	Inhibiting cancer progression
	CCA	Reduce progression of CCA cells both in vivo and in vitro
	HB	Regulating the expression and half-life period of c-MYC genes
	Melanoma	Inducing tumor cell cycle arrest and apoptosis in vitro
UNC0642	BCa, cancer, melanoma	Induces gene expression related to RS stress and ROS production
	Melanoma	Inducing melanoma cell death
	Melanoma

Abbreviations: BCa, breast cancer; CCA, cholangiocarcinoma; HB, hepatoblastoma; HCC, hepatocellular carcinoma; MM, multiple myeloma.

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