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Published on: September 8, 2017
Let-7a Could Serve as A Biomarker for Chemo-Responsiveness to Docetaxel in Gastric Cancer
Najibeh Shekari1,2,3, Faezeh Asghari1,2, Navideh Haghnavaz1,2
1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Background:
MicroRNAs are noncoding RNAs which play critical roles in response to anti-cancer agents. Let-7a and miR-21 are well-known tumor-suppressor and oncomiR miRNAs, respectively. They are involved in tumorigenesis of gastric cancer and have potential to be used as markers in response to the therapy.
Objective:
We aimed to study alterations in the expression of Let-7a and miR-21, and their targets in gastric cancer cell lines after treatment with docetaxel.
Methods:
In order to determine the IC50 of docetaxel, MTT assay was performed in AGS, MKN45 and KATO III gastric cancer cell lines. The expression levels of Let-7a and miR-21 and their target genes, HMGA2 and PDCD4, were determined by reverse-transcription quantitative real-time PCR for both treated and untreated cell lines.
Results:
MTT assay showed higher IC50 concentration of docetaxel in KATO III in comparison with AGS and MKN45, indicating KATO III`s higher resistance to docetaxel. Following the treatment, the expression level of Let-7a was significantly increased in AGS and MKN45, while decreased in KATO III. Expression level of miR- 21 in the three treated cell lines was increased significantly. Not only Let-7a, but also expression level of HMGA2 and PDCD4 genes showed different patterns in KATO III in comparison with AGS and MKN45.
Conclusion:
Down-regulation and up-regulation of Let-7a in docetaxel-resistant and sensitive cell lines, respectively indicates its potential usefulness as biomarker for responsiveness of gastric cancer to the therapy with docetaxel and also for predicting patient`s outcome.
Insights
Let-7a microRNA levels changed differently in gastric cancer cells treated with docetaxel, suggesting its potential as a biomarker for predicting treatment response and patient outcomes.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs regulate gene expression and are crucial in cancer development.
- Let-7a acts as a tumor suppressor, while miR-21 is an oncomiR, both implicated in gastric cancer.
- These microRNAs show potential as predictive biomarkers for anti-cancer therapy response.
Purpose of the Study:
- To investigate the expression changes of Let-7a and miR-21 in gastric cancer cell lines post-docetaxel treatment.
- To analyze the expression patterns of their target genes, HMGA2 and PDCD4.
- To evaluate the potential of Let-7a as a biomarker for docetaxel responsiveness in gastric cancer.
Main Methods:
- Gastric cancer cell lines (AGS, MKN45, KATO III) were treated with docetaxel.
- Drug sensitivity was assessed using MTT assay to determine IC50 values.
- Expression levels of Let-7a, miR-21, HMGA2, and PDCD4 were quantified using RT-qPCR.
Main Results:
- KATO III cells exhibited higher docetaxel resistance (higher IC50) compared to AGS and MKN45 cells.
- Let-7a expression increased in docetaxel-sensitive AGS and MKN45 cells but decreased in resistant KATO III cells.
- miR-21, HMGA2, and PDCD4 showed distinct expression patterns across cell lines following docetaxel treatment.
Conclusions:
- Differential expression of Let-7a in response to docetaxel suggests its utility as a biomarker for gastric cancer therapy responsiveness.
- Let-7a levels may help predict patient outcomes in docetaxel-treated gastric cancer.
- Understanding microRNA alterations provides insights into chemoresistance mechanisms.
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