Related Experiment Video

Updated: Jun 12, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma

Jaehyouk Lee1, Dong-Jun Jeong, Jinsun Kim

  • 1Research Center for Women's Diseases and Division of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.

Molecular Cancer
|May 21, 2010
PubMed
Abstract

Insights

Epigenetic silencing of the Klotho gene, a Wnt antagonist, occurs in cervical cancer. This silencing contributes to Wnt pathway activation and tumor growth, suggesting Klotho as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Klotho, initially identified as an anti-aging gene, also functions as a tumor suppressor and secreted Wnt antagonist.
  • Epigenetic silencing of Wnt antagonists is common in cancers.
  • Aberrant Wnt pathway activation due to epigenetic deregulation of Wnt antagonists is implicated in cervical tumorigenesis.

Purpose of the Study:

  • To investigate the epigenetic silencing of the KLOTHO gene in human cervical carcinoma.
  • To determine the role of KLOTHO in cervical tumorigenesis.

Main Methods:

  • Analysis of KLOTHO mRNA expression in cervical cancer cell lines and patient samples.
  • Treatment with DNA demethylating agent (2'-deoxy-5-azacytidine) and histone deacetylase inhibitor (trichostatin A).
  • Methylation-specific PCR and bisulfite genomic sequencing of the KLOTHO promoter.
  • Analysis of histone deacetylation in the SiHa cell line.
  • Ectopic expression of secreted KLOTHO in CaSki cells to assess Wnt signaling and clonogenic activity.

Main Results:

  • KLOTHO mRNA loss was observed in cervical cancer cell lines and invasive carcinomas, but not in preinvasive lesions.
  • KLOTHO mRNA expression was restored by demethylating agents and histone deacetylase inhibitors.
  • CpG hypermethylation and histone deacetylation were identified as mechanisms of KLOTHO silencing.
  • Ectopic KLOTHO expression suppressed Wnt signaling, reduced active beta-catenin, and inhibited colony growth.

Conclusions:

  • Epigenetic silencing of KLOTHO occurs during the late stages of cervical tumorigenesis.
  • Loss of KLOTHO function as a Wnt antagonist contributes to Wnt pathway activation in cervical cancer.
  • KLOTHO represents a potential target for cervical cancer therapy.

Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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...