Related Experiment Video

Updated: Jun 11, 2025

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization
06:01

Clinicopathological Analysis of miRNA Expression in Breast Cancer Tissues by Using miRNA In Situ Hybridization

Published on: June 7, 2016

6.7K

miRNAs in Signal Transduction of SMAD Proteins in Breast Cancer

Tomasz Sirek1,2, Agata Sirek1,2, Przemysław Borawski3

  • 1Department of Plastic and Reconstructive Surgery, Hospital for Minimally Invasive and Reconstructive Surgery in Bielsko-Biała, 43-316 Bielsko-Biala, Poland.

International Journal of Molecular Sciences
|September 28, 2024
PubMed

Insights

This study identified microRNAs (miRNAs) regulating SMAD proteins in Polish breast cancer patients. Overexpressed SMADs and reduced SMAD7 suggest increased TGFβ pathway activity, potentially driving tumor growth, especially in aggressive subtypes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The transforming growth factor beta (TGFβ) signaling pathway, mediated by SMAD proteins, plays a crucial role in breast cancer development and progression.
  • Dysregulation of SMAD protein activity and their regulatory microRNAs (miRNAs) is implicated in various cancer types.
  • Understanding these molecular mechanisms is vital for identifying potential therapeutic targets in breast cancer.

Purpose of the Study:

  • To identify specific miRNAs that regulate SMAD protein activity in five distinct breast cancer subtypes.
  • To investigate the expression profiles of SMAD genes and their associated miRNAs in breast cancer tissues from Polish women.
  • To correlate SMAD and miRNA expression patterns with breast cancer subtypes and potential pathway activation.

Main Methods:

  • Analysis of gene expression for SMAD proteins using mRNA microarrays and RT-qPCR.
  • Quantification of SMAD protein levels via ELISA.
  • miRNA profiling using miRNA microarrays and database analysis (miRDB).
  • Inclusion of patient cohorts representing luminal A, luminal B HER2-, luminal B HER2+, non-luminal HER2+, and triple-negative breast cancer (TNBC).

Main Results:

  • SMAD3 and SMAD5 were overexpressed across all breast cancer subtypes, potentially linked to reduced miR-145 expression.
  • SMAD4 and miR-155 showed similar overexpression patterns.
  • SMAD7 expression was reduced, possibly due to low activity of miR-15b and miR21b.
  • Overexpression of SMAD3, SMAD4, and SMAD5 indicates excessive TGFβ pathway activation.
  • Reduced SMAD7 expression suggests a loss of inhibitory control over the TGFβ pathway, particularly in aggressive breast cancers.

Conclusions:

  • This study elucidates the gene expression profiles of SMAD proteins and identifies regulatory miRNAs in different breast cancer subtypes.
  • The findings suggest that dysregulated SMAD signaling, driven by specific miRNA interactions, contributes to breast cancer progression.
  • Targeting these miRNA-SMAD interactions could offer novel therapeutic strategies for breast cancer treatment.
Keywords:
SMADbreast cancermiRNAtransforming growth factor beta

More Related Videos

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

20.2K
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.8K

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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...
3.8K
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...
4.5K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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...
7.3K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.7K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.4K