Related Experiment Video
Updated: Feb 5, 2026
Primary Human Bronchial Epithelial Cells Grown from Explants
Published on: March 26, 2010
Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic through STAT3/miR-301a/SMAD4 Loop
Mingtian Zhong1, Zhujuan Huang1, Lei Wang2,3
1The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Abstract:
Arsenic is a well-known of human carcinogen and miR-301a is an oncogenic microRNA, which links to oncogenesis, however, little is understood about its contribution to arsenic-induced cellular transformation and tumorigenesis. Here, we investigated the role of miR-301a during arsenic-induced cellular transformation and tumor formation. miR-301a was found to be upregulated during arsenic-induced BEAS-2B transformation and the overexpression of miR-301a was dependent on IL-6/STAT3 signaling. Inhibition of miR-301a leads to reduction of cell proliferation, colony formation and cell migration. By using dual luciferase assay, SMAD4 was confirmed to be a direct target of miR-301a in BEAS-2B cells and upregulation of SMAD4 is involved the restraining cell growth and migration. In addition, reducing of miR-301a expression enhances doxorubicin-induced cellular apoptosis of transformed BEAS-2B through up-regulating SMAD4. Furthermore, we demonstrated that downregulation of miR-301a in BEAS-2B attenuates tumor growth in the xenograft model by targeting SMAD4. Of note, the level of miR-301a expression correlated inversely with SMAD4 expression in clinical specimens of human lung cancer. Our findings ascertain that miR-301a is an oncogenic miRNA, which targets SMAD4 to establish an essential mechanism for arsenic-induced carcinogenesis, IL-6/STAT3/miR-301a/SMAD4 signaling pathways.
Insights
Arsenic exposure increases miR-301a, a microRNA that promotes cancer by targeting SMAD4. Inhibiting miR-301a reduces tumor growth and enhances apoptosis, revealing a key pathway in arsenic-induced carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Environmental Health
Background:
- Arsenic is a known human carcinogen.
- MicroRNA-301a (miR-301a) is implicated in oncogenesis.
- The role of miR-301a in arsenic-induced cancer is unclear.
Purpose of the Study:
- Investigate miR-301a's role in arsenic-induced cellular transformation and tumor formation.
- Elucidate the molecular mechanisms linking miR-301a, arsenic, and cancer.
- Identify potential therapeutic targets for arsenic-induced cancers.
Main Methods:
- Studied miR-301a expression in arsenic-transformed BEAS-2B cells.
- Utilized IL-6/STAT3 signaling pathway analysis.
- Performed dual luciferase assays to identify miR-301a targets.
- Assessed effects of miR-301a inhibition on cell proliferation, migration, and apoptosis.
- Evaluated tumor growth in a xenograft model.
- Analyzed miR-301a and SMAD4 expression in clinical lung cancer samples.
Main Results:
- miR-301a was upregulated in arsenic-transformed cells, dependent on IL-6/STAT3 signaling.
- SMAD4 was identified as a direct target of miR-301a.
- Inhibiting miR-301a reduced cell proliferation, colony formation, and migration.
- Downregulating miR-301a enhanced doxorubicin-induced apoptosis by upregulating SMAD4.
- Reduced miR-301a expression attenuated tumor growth in vivo.
- Inverse correlation between miR-301a and SMAD4 expression in human lung cancer.
Conclusions:
- miR-301a acts as an oncogenic miRNA in arsenic-induced carcinogenesis.
- The IL-6/STAT3/miR-301a/SMAD4 pathway is crucial for arsenic-induced cancer.
- miR-301a targets SMAD4 to promote cell growth and migration.
- Targeting miR-301a or modulating SMAD4 may offer therapeutic strategies for arsenic-related lung cancers.
More Related Videos
Related Concept Videos
01:23The Bronchial Tree
The trachea, commonly known as the windpipe, is a tube that connects the larynx (voice box) to the bronchi. At a point called the carina, it bifurcates into two primary bronchi. The right primary bronchus is wider, shorter, and more vertical than the left primary...
01:33Bacterial Transformation
Griffith made an unexpected discovery when he killed the pathogenic strain and mixed its remains with the live, non-pathogenic strain. Not only did the mixture kill host mice, but it also contained living pathogenic bacteria that...
01:07Cell Signaling Feedback Loops
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...
01:01Feedback Loops
01:26Transformers
The iron core has a substantial relative permeability. Therefore, the magnetic field lines generated due to the current in one winding are almost entirely confined within the core, such that the same magnetic flux permeates each turn of both...
01:26Transformation