Effect of miR-4270 on Tumorigenicity in Gastric Cancer Stem Cells via the Wnt Signaling Pathway
Hassan Akrami1, Behrouz Moradi2, Kiumars Mehdizadeh2
1Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Background:
Cancer stem cells and miRNAs are the most important factors in the tumorigenicity of cancers. So, we evaluated the properties of gastric cancer stem-like cells (GCSCs) under treatment using a hsa-miR-4270 inhibitor and a mimic.
Materials And Methods:
We isolated GCSCs from the MKN-45 cell line using a non-adherence surface method. Then, GCSCs were treated with hsa-miR-4270 inhibitor/mimic with different concentrations, and the cell proliferation was measured with the MTT assay to find the suitable concentration of inhibitor/mimic for following experiments. Apoptosis, angiogenesis, and metastasis were evaluated by DNA laddering, tube formation, zymography and Transwell assay, respectively. Transcription of the genes in Wnt1 signaling was measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Protein levels of Wnt1, CTNNB1P1, and SMARCD1 were evaluated by western blotting, and interactions between genes involved in our study were examined by STRING and Gene mania tools.
Results:
The results showed that the hsa-miR-4270 inhibitor declined cell proliferation, MMP activity, migration, and angiogenesis, and induced apoptosis. However, the hsa-miR-4270 mimic had opposite effects on those cell functions. The results of the effects of hsa-miR-4270 inhibitor/mimic on the Wnt1 signaling pathway revealed that the arrest of miR-4270 could inhibit the canonical Wnt1 signaling pathway.
Conclusions:
In summary, hsa-miR-4270 is an oncomir in the tumorigenicity of GC stem cells, which may be considered an appropriate candidate for GC treatment.
Insights
Hsa-miR-4270 acts as an oncomir in gastric cancer stem cells. Inhibiting hsa-miR-4270 reduces tumor growth and metastasis, suggesting its potential as a therapeutic target for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Gastric cancer stem cells (GCSCs) and microRNAs (miRNAs) are key factors in cancer development.
- This study investigates the role of hsa-miR-4270 in GCSC properties.
Purpose of the Study:
- To evaluate the effects of hsa-miR-4270 inhibition and mimicry on GCSCs.
- To determine if hsa-miR-4270 influences the Wnt1 signaling pathway.
Main Methods:
- GCSCs were isolated and treated with hsa-miR-4270 inhibitor/mimic.
- Assays included MTT for proliferation, DNA laddering for apoptosis, tube formation for angiogenesis, and Transwell for migration.
- Gene expression (RT-PCR) and protein levels (Western blotting) of Wnt1 pathway components were analyzed.
Main Results:
- Hsa-miR-4270 inhibition decreased proliferation, MMP activity, migration, and angiogenesis, while inducing apoptosis.
- Hsa-miR-4270 mimicry showed opposite effects.
- Inhibition of hsa-miR-4270 suppressed the canonical Wnt1 signaling pathway.
Conclusions:
- Hsa-miR-4270 functions as an oncomir in gastric cancer stem cells.
- Targeting hsa-miR-4270 presents a potential therapeutic strategy for gastric cancer treatment.
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