Related Experiment Video

Updated: Dec 23, 2025

Isolation of CD133+ Liver Stem Cells for Clonal Expansion
12:06

Isolation of CD133+ Liver Stem Cells for Clonal Expansion

Published on: October 10, 2011

22.7K

The DNMT1/miR-34a/FOXM1 Axis Contributes to Stemness of Liver Cancer Cells

Xiaocheng Cao1,2,3, Lihua Liu4,5, Xiaozheng Cao4,5

  • 1Key Laboratory of Study and Discover of Small Targeted Molecules of Hunan Province, Medical College, Hunan Normal University, Changsha, Hunan 410013, China.

Journal of Oncology
|April 21, 2020
PubMed
Abstract

Insights

Aberrant DNA methyltransferase 1 (DNMT1) activates liver cancer stem cells (LCSCs) by silencing miR-34a, leading to FoxM1 upregulation and promoting stemness. Targeting this DNMT1/miR-34a pathway may suppress liver cancer.

Area of Science:

  • Molecular Biology
  • Cancer Stem Cell Biology
  • Epigenetics

Background:

  • Liver cancer stem cells (LCSCs) possess self-renewal and differentiation capabilities, driving tumor initiation and recurrence.
  • The role of DNA methyltransferase 1 (DNMT1)/miR-34a/FoxM1 signaling in LCSC stemness remains incompletely understood.

Purpose of the Study:

  • To investigate whether DNMT1-mediated methylation of miR-34a contributes to LCSC stemness through FoxM1 upregulation.

Main Methods:

  • Utilized CD133+ MHCC97H cells as LCSCs.
  • Quantified gene and microRNA expression via qRT-PCR.
  • Assessed protein levels using immunoblotting.
  • Evaluated stemness properties through sphere and colony formation assays, and flow cytometry.
  • Investigated in vivo oncogenicity in a mouse xenograft model.
  • Manipulated DNMT1 and miR-34a levels using lentiviral systems.
  • Confirmed FoxM1 as a miR-34a target using a reporter assay.

Main Results:

  • LCSCs showed higher DNMT1, lower miR-34a, and increased stemness compared to parental cells.
  • DNMT1 knockdown reduced DNMT1, increased miR-34a, and decreased stemness.
  • miR-34a mimic transfection suppressed LCSC stemness, while miR-34a inhibitor enhanced it.
  • FoxM1 was identified as a direct target of miR-34a in LCSCs.

Conclusions:

  • Aberrant DNMT1 activation leads to miR-34a promoter methylation, suppressing miR-34a and upregulating FoxM1, thereby promoting LCSC stemness.
  • Inhibition of the DNMT1/miR-34a-FoxM1 axis presents a potential therapeutic strategy for liver cancer targeting LCSCs.

More Related Videos

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

801
Generation of Subcutaneous and Intrahepatic Human Hepatocellular Carcinoma Xenografts in Immunodeficient Mice10:35

Generation of Subcutaneous and Intrahepatic Human Hepatocellular Carcinoma Xenografts in Immunodeficient Mice

Published on: September 25, 2013

36.9K

Related Concept Videos

Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.8K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
9.6K
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...
5.0K
Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
4.1K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.1K
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.2K