Related Experiment Video
Updated: Jun 5, 2026
Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Senescence-associated gene YPEL3 is downregulated in human colon tumors
Rebecca Tuttle1, Margo Simon, David C Hitch
1Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA.
Background:
Previous work has demonstrated YPEL3 to be a growth-suppressive protein that acts through a pathway of cellular senescence. We set out to determine whether human colon tumors demonstrated downregulation of YPEL3.
Methods:
We collected colon tumor samples with matched normal control samples and analyzed them for YPEL3 gene expression by reverse transcriptase-polymerase chain reaction and CpG hypermethylation of the YPEL3 promoter by base-specific polymerase chain reaction analysis. Colon cancer cell lines (Caco-2 and HCT116(-/-) p53) were used to assess YPEL3 gene expression after treatment with 5-azadeoxycytidine or trichostatin A.
Results:
Reverse transcriptase-polymerase chain reaction analysis demonstrated a decrease in YPEL3 expression in tumor samples when compared to their patient-matched normal tissue. We determined that DNA methylation of the YPEL3 promoter CpG island does not play a role in YPEL3 regulation in human colon tumors or colon cancer cells lines, consistent with the inability of 5-azadeoxycytidine treatment to induce YPEL3 expression in colon cancer cell lines. In contrast, colon cell line results suggest that histone acetylation may play a role in YPEL3 regulation in colon cancer.
Conclusions:
YPEL3 is preferentially downregulated in human colon adenocarcinomas. DNA hypermethylation does not appear to be the mechanism of YPEL3 downregulation in this subset of collected patient samples or in colon cell lines. Histone acetylation may be a relevant epigenetic modulator of YPEL3 in colon adenocarcinomas. Future investigation of YPEL3 and its role in colon cancer signaling and development may lead to increased understanding and alternative treatment options for this disease.
Insights
YPEL3 protein is downregulated in human colon adenocarcinomas. DNA hypermethylation is not the cause; histone acetylation may regulate YPEL3, offering potential new colon cancer treatment avenues.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- YPEL3 functions as a growth-suppressive protein.
- YPEL3 is implicated in cellular senescence pathways.
- Previous research suggests YPEL3's role in cancer suppression.
Purpose of the Study:
- To investigate YPEL3 downregulation in human colon tumors.
- To explore the epigenetic mechanisms behind YPEL3 regulation in colon cancer.
Main Methods:
- Analyzed YPEL3 gene expression in colon tumor and normal tissues using RT-PCR.
- Assessed YPEL3 promoter CpG hypermethylation via base-specific PCR.
- Examined YPEL3 expression in colon cancer cell lines after treatment with epigenetic modifiers (5-azadeoxycytidine, trichostatin A).
Main Results:
- YPEL3 expression was significantly decreased in colon tumor samples compared to matched normal tissues.
- DNA hypermethylation of the YPEL3 promoter was not found to be a mechanism for YPEL3 downregulation.
- Results suggest histone acetylation may play a role in YPEL3 regulation in colon cancer cell lines.
Conclusions:
- YPEL3 is preferentially downregulated in human colon adenocarcinomas.
- Epigenetic mechanisms like DNA hypermethylation do not drive YPEL3 downregulation in this context.
- Histone acetylation emerges as a potential epigenetic regulator of YPEL3 in colon adenocarcinomas, warranting further investigation for therapeutic strategies.
Related Concept Videos
02:23Abnormal Proliferation
01:12Loss 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...
01:12Loss 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...
01:05Cancer-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...
01:05Cancer-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...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...