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Updated: Jun 16, 2025

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Epigenetic alterations of TP53INP1 by EHMT2 regulate the cell cycle in gastric cancer
Tae Young Ryu1, In Hwan Tae1, Tae-Su Han1,2,3
1Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.
Background:
Gastric cancer (GC) is a type of cancer with high incidence and mortality rates. Although various chemical interventions are being developed to treat gastric cancer, there is a constant demand for research into new GC treatment targets and modes of action (MOAs) because of the low effectiveness and side effects of current treatments.
Methods:
Using the TCGA data portal, we identified EHMT2 overexpression in GC samples. Using RNA-seq and EHMT2-specific siRNA, we investigated the role of EHMT2 in GC cell proliferation and validated its function with two EHMT2-specific inhibitors. Through the application of 3D spheroid culture, patient-derived gastric cancer organoids (PDOs), and an in vivo model, we confirmed the role of EHMT2 in GC cell proliferation.
Results:
In this study, we found that EHMT2, a histone 3 lysine 9 (H3K9) methyltransferase, is significantly overexpressed in GC patients compared with healthy individuals. Knockdown of EHMT2 with siRNA induced G1 cell cycle arrest and attenuated GC cell proliferation. Furthermore, we confirmed that TP53INP1 induction by EHMT2 knockdown induced cell cycle arrest and inhibited GC cell proliferation. Moreover, specific EHMT2 inhibitors, BIX01294 and UNC0638, induced cell cycle arrest in GC cell lines through TP53INP1 upregulation. The efficacy of EHMT2 inhibition was further confirmed in a 3D spheroid culture system, PDOs, and a xenograft model.
Conclusions:
Our findings suggest that EHMT2 is an attractive therapeutic target for GC treatment.
Insights
EHMT2 is overexpressed in gastric cancer (GC) and inhibiting it halts cancer cell proliferation. This histone methyltransferase is a promising new therapeutic target for effective GC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer (GC) presents high incidence and mortality rates, necessitating novel therapeutic targets due to limitations of current treatments.
- Existing chemical interventions for GC often exhibit low effectiveness and significant side effects.
- Research into new GC treatment targets and mechanisms of action (MOAs) is crucial.
Discussion:
- EHMT2 (Euclidean distance metric learning, Mahalanobis-distance based, k-nearest neighbors, and transfer learning) was identified as significantly overexpressed in GC patient samples via TCGA data.
- EHMT2 functions as a histone 3 lysine 9 (H3K9) methyltransferase.
- Knockdown of EHMT2 using siRNA resulted in G1 cell cycle arrest and reduced GC cell proliferation.
Key Insights:
- EHMT2 knockdown induces TP53INP1, leading to cell cycle arrest and inhibited proliferation.
- Specific EHMT2 inhibitors, BIX01294 and UNC0638, also upregulate TP53INP1, causing cell cycle arrest in GC cell lines.
- Validated EHMT2's role in GC proliferation using 3D spheroid culture, patient-derived gastric cancer organoids (PDOs), and an in vivo xenograft model.
Outlook:
- EHMT2 inhibition demonstrates efficacy across multiple experimental models, including organoids and xenografts.
- The findings highlight EHMT2 as a potential therapeutic target for gastric cancer.
- Further investigation into EHMT2-targeted therapies could lead to improved GC treatment strategies.
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