Inhibition of Euchromatic Histone Lysine Methyltransferase 2 (EHMT2) Suppresses the Proliferation and Invasion of Cervical Cancer Cells

Abstract

EHMT2 (euchromatic histone lysine methyltransferase 2), a histone methyltransferase, has been shown to be involved in multiple human cancers. In this study, we determined mRNA and protein expression of EHMT2 in cervical cancer cells and normal cervical epithelial cells. EHMT2 was inhibited with short hairpin RNA (shEHMT2) in cervical cancer cells. Cell viability, colony proliferation, apoptosis, adhesion, and invasion assays and Western blot were performed to assess the function of EHMT2. As a result, EHMT2 was upregulated in human cervical cancer cells compared to normal cervical epithelial cells. Suppression of EHMT2 expression impairs cell proliferation and induces apoptosis. Furthermore, EHMT2 silencing inhibited cell adhesion and invasion. Finally, knockdown of EHMT2 resulted in a reduction of the expression of the tumorigenic proteins Bcl-2, Mcl-1, and Survivin and in an increase in the expression of the anti-malignant protein E-cadherin. In conclusion, our data suggest that EHMT2 plays a key role in cell proliferation and metastatic capacity in cervical cancer cells and could serve as a potential therapeutic target.

Structure, Activity, and Function of the Protein Lysine Methyltransferase G9a

“…These epigenetic modifications, which result in altered chromatin structure and gene expression were reported in different types of cancers [ 108 ] ( Figure 3 ). G9a was overexpressed in breast, gastric, ovarian, cervical, endometrial, prostate, lung, colorectal, liver, urinary bladder, and brain cancers, as well as in hematological malignancies, melanoma, and cholangiocarcinoma, leading to aberrant H3K9 methylation [ 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ]. One of the main reasons for this increase in G9a expression and H3K9 methylation is hypoxia [ 103 ].…”

“…In cervical cancer, G9a induces the expression of angiogenic factors including angiogenin, interleukin-8, and C-X-C motif chemokine ligand-16, prompting angiogenesis and cancer cell invasion, and decreasing patient survival [ 142 ]. Interestingly, depletion of G9a decreased the expression of oncogenic proteins such as Bcl-2, Mcl-1, and Survivin, and increased the expression of E-cadherin inhibiting cell adhesion and invasion [ 112 ].…”

GMDS Intragenic Deletions Associate with Congenital Heart Disease including Ebstein Anomaly

“…An array-CGH was performed. The Agilent Bench Lab CNV Version 5.1 180 K array-CGH showed a de novo deletion on chromosome 6p25.3 of ~403 kb (Figure 2) and a maternally inherited duplication in Xq27.2 of ~316 kb (arr [GRCh37] 6p25.3(1727928_2131157) x1 dn, Xq27.2(140693307_141009050) x3 mat, in accordance with the ISCN 2020 nomenclature [18]. No (likely) pathogenic variants were identified in the NGS gene panel.…”

EHMT1/EHMT2 in EMT, cancer stemness and drug resistance: emerging evidence and mechanisms

“…Human cervical cancer cell lines (CaloGR) exhibit high levels of EHMT2 as compared to cervical epithelial cells. Loss‐of‐function studies indicated a reduction in cell adhesion and invasive capacities through downregulation of E‐cadherin [38]. Pharmacological and genetic inhibition of EHMT2 impeded angiogenesis, invasion and migration both in vitro and in vivo , with a reduction in the expression of angiogenic genes including CXCL16, IL‐8, VEGF, MMP9, MCP‐1, Pentraxin‐3, GM‐CSF, Serpin E1,TIMP‐1, TIMP‐4 and Thrombospondin‐1 [39].…”