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Let-7a Could Serve as A Biomarker for Chemo-Responsiveness to Docetaxel in Gastric Cancer

[ Vol. 19 , Issue. 3 ]

Author(s):

Najibeh Shekari, Faezeh Asghari, Navideh Haghnavaz, Dariush Shanehbandi, Vahid Khaze, Behzad Baradaran and Tohid Kazemi*   Pages 304 - 309 ( 6 )

Abstract:


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.

Keywords:

Gastric cancer, docetaxel, Let-7a, miR-21, chemoresistance, chemosensitivity.

Affiliation:

Tabriz University of Medical Sciences - Immunology Tabriz, Tabriz University of Medical Sciences - Immunology Tabriz, Tabriz University of Medical Sciences - Immunology Tabriz, Tabriz University of Medical Sciences - Immunology Tabriz, Tabriz University of Medical Sciences - Immunology Tabriz, Tabriz University of Medical Sciences - Immunology Tabriz, Tabriz University of Medical Sciences - Immunology Tabriz



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