Related Experiment Video

Updated: Dec 28, 2025

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

2.1K

MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response

Huan Qiu1, Bang-Ming Jin1, Zhan-Feng Wang2

  • 1Department of Basic Medical Sciences, School of Medicine, Xiamen University, Xiamen, 361102, Fujian Province, People's Republic of China.

Nature Communications
|February 22, 2020
PubMed

Insights

Loss of the MEN1 gene in mice leads to DNA damage and promotes lung tumorigenesis by counteracting tumor-suppressing mechanisms. This finding has implications for understanding neuroendocrine lung cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The MEN1 gene, encoding the tumor suppressor protein menin, is frequently mutated in neuroendocrine (NE) tumors.
  • The role of MEN1 in NE-type lung cancer development in vivo is not well understood.

Purpose of the Study:

  • To investigate the biological significance of menin deficiency in lung tumorigenesis.
  • To explore the impact of menin loss on oncogenic Kras signaling and tumor progression in a mouse model.

Main Methods:

  • Establishment of a genetically engineered mouse model (ATII-specific KrasG12D/+/Men1-/-).
  • Analysis of DNA damage accumulation, senescence, and epithelial-to-mesenchymal transition (EMT).
  • Correlation of menin loss with NE profiles and survival in human lung cancer samples.

Main Results:

  • Menin deficiency leads to increased DNA damage accumulation in lung tumors.
  • Loss of menin antagonizes oncogenic Kras-induced senescence.
  • Menin deficiency promotes epithelial-to-mesenchymal transition (EMT) during lung tumorigenesis.
  • Reduced menin expression in human lung cancers correlates with higher NE markers and poorer survival.

Conclusions:

  • Menin plays a critical role in suppressing lung tumorigenesis by maintaining genomic stability and counteracting oncogenic Kras-driven processes.
  • Loss of menin function contributes to the development of NE-type lung cancers.
  • Menin status may serve as a prognostic biomarker in lung cancer.

More Related Videos

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

2.9K
Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens09:33

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens

Published on: August 25, 2023

1.5K

Related Concept Videos

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
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...
5.7K
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
6.2K
Mismatch Repair01:36

Mismatch Repair

Overview
43.4K
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
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
4.8K