Related Experiment Video

Updated: May 6, 2026

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
09:16

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells

Published on: September 1, 2019

6.6K

Runx3 inactivation is a crucial early event in the development of lung adenocarcinoma

You-Soub Lee1, Jung-Won Lee, Ju-Won Jang

  • 1Department of Biochemistry, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea.

Cancer Cell
|November 16, 2013
PubMed

Insights

Runx3 inactivation promotes lung adenocarcinoma in mice and humans. Runx3-BRD2 complex formation, induced by oncogenic K-Ras, regulates cell cycle genes involved in tumor suppression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Runx3 is a tumor suppressor gene.
  • Oncogenic K-Ras is a common driver mutation in lung cancer.
  • The precise mechanisms linking K-Ras activation to tumor suppression pathways are not fully understood.

Purpose of the Study:

  • To investigate the role of Runx3 in K-Ras-driven lung tumorigenesis.
  • To elucidate the molecular mechanisms by which Runx3 and K-Ras interact.
  • To identify potential therapeutic targets for lung adenocarcinoma.

Main Methods:

  • Targeted inactivation of Runx3 in mouse lung models.
  • Analysis of human lung adenocarcinoma samples with K-RAS mutations.
  • Functional genetic screening in Drosophila.
  • Molecular analysis of cell lines.

Main Results:

  • Runx3 inactivation accelerated K-Ras-induced lung adenocarcinoma formation in mice.
  • RUNX3 was frequently inactivated in human K-RAS mutated lung adenocarcinomas.
  • Runx3 forms a complex with BRD2 in a K-Ras-dependent manner.
  • This complex regulates the expression of cell cycle inhibitors p14(ARF) and p21(WAF/CIP).
  • Constitutive K-Ras activation led to stable Runx3-BRD2 complex formation and prolonged p14(ARF)/p19(Arf) and p21(WAF/CIP) expression.

Conclusions:

  • Runx3 acts as a tumor suppressor in K-Ras-driven lung cancer.
  • The Runx3-BRD2 complex is a key mediator linking oncogenic K-Ras to the p14(ARF)-p53 pathway.
  • These findings provide insights into cellular defense mechanisms against oncogenic K-Ras and suggest potential therapeutic strategies.

More Related Videos

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

6.8K
Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression07:53

Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression

Published on: March 17, 2020

6.6K

Related Concept Videos

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...
6.0K
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...
7.5K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
5.7K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
12.5K
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.
28.8K
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...
3.5K