Related Experiment Video
Updated: Jul 2, 2026

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation
Yan Cui1, Ying Ying, Andrew van Hasselt
1State Key Laboratory in Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute, Chinese University of Hong Kong, Hong Kong, China.
Background:
Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common in multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction.
Methodology/Principal Findings:
Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -independent growth of carcinoma cells with endogenous silencing.
Conclusions/Significance:
Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies.
Insights
We identified OPCML as a broad tumor suppressor gene. Its silencing by methylation is frequent in many cancers, impacting tumor growth and stress response.
Area of Science:
- Epigenetics and Cancer Biology
- Tumor Suppressor Gene Identification
Background:
- CpG methylation-silenced tumor suppressor genes (TSGs) are key to tumorigenesis and serve as biomarkers.
- Loss of heterozygosity at 11q25 is common in various tumors, including nasopharyngeal carcinoma (NPC).
- OPCML, located at 11q25, was identified as a downregulated gene via digital expression subtraction.
Purpose of the Study:
- To investigate the role of OPCML in tumorigenesis.
- To determine the mechanism of OPCML downregulation.
- To assess OPCML's potential as a tumor suppressor across multiple cancer types.
Main Methods:
- Semi-quantitative RT-PCR to assess OPCML expression.
- Multiplex differential DNA-PCR to detect homozygous deletions.
- Promoter methylation analysis in various cancer cell lines and primary tumors.
- Demethylation studies (pharmacological and genetic) to confirm epigenetic silencing.
- Ectopic expression of OPCML in cancer cells.
Main Results:
- Frequent OPCML silencing was observed in NPC and other common tumors, without homozygous deletions.
- Promoter methylation of OPCML was detected in multiple carcinoma and lymphoma cell lines, but not in non-tumor cell lines.
- Demethylation restored OPCML expression, confirming epigenetic silencing.
- OPCML's stress-responsive function is impaired by promoter methylation.
- Ectopic OPCML expression inhibited carcinoma cell growth.
Conclusions:
- OPCML is identified as a broad tumor suppressor gene.
- Frequent inactivation of OPCML by promoter methylation occurs across multiple malignancies.
- OPCML methylation represents a significant epigenetic mechanism in cancer development.
Related Concept Videos
Abnormal Proliferation
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Induced Pluripotent Stem Cells
Somatic cells are...