Related Experiment Video
Updated: Apr 4, 2026
06:54
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
14.8K
An epigenetic auto-feedback loop regulates TGF-β type II receptor expression and function in NSCLC
Shanzhong Yang1,2, Yong-Jig Cho3, Lin Jin1,2
1Division of Hematology and Oncology, Department of Medicine, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Oncotarget
|September 11, 2015
Summary
Lung cancer progression involves decreased transforming growth factor-β (TGF-β) type II receptor (TβRII). This study reveals a feedback loop involving miR-145, c-Myc, and miR-20a that regulates TβRII, impacting TGF-β tumor suppressor functions.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Transforming growth factor-β (TGF-β) type II receptor (TβRII) downregulation is crucial in lung cancer progression.
- MicroRNAs (miRNAs) are key regulators of oncogenes and tumor suppressor genes.
Purpose of the Study:
- To investigate the role of miRNAs in regulating TβRII expression in non-small cell lung cancer (NSCLC).
- To elucidate the feedback loop mechanism involving miRNAs and proteins affecting TGF-β signaling in lung cancer.
Main Methods:
- miRNA microarray, northern blot, and quantitative reverse transcription PCR (QRT-PCR) analysis.
- In vivo tumorigenicity assays in lung cancer cells.
- Analysis of The Cancer Genome Atlas (TCGA) public database for NSCLC specimens.
Main Results:
- An inverse correlation between miR-20a and TβRII expression was observed in NSCLC.
- miR-20a directly downregulates TβRII, inhibiting TGF-β signaling and promoting lung cancer cell growth.
- miR-145, induced by TGF-β, targets c-Myc to inhibit miR-20a, thereby upregulating TβRII and restoring tumor suppressor functions.
Conclusions:
- A novel feedback loop (TGF-β/miR-145/c-Myc/miR-20a/TβRII) regulates TβRII expression and TGF-β tumor suppressor activity in NSCLC.
- This mechanism offers potential therapeutic targets for lung cancer treatment.
Related Concept Videos
01:16TGF - β Signaling Pathway
11.0K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
11.0K
03:03mTOR Signaling and Cancer Progression
5.1K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
5.1K
01:07Cell Signaling Feedback Loops
8.0K
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
8.0K
01:24Regulation of Angiogenesis and Blood Supply
4.0K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
4.0K
01:23Negative Regulator Molecules
39.0K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
39.0K
02:26NF-κB-dependent Signaling Pathway
10.3K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
10.3K