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

Author(s): Najibeh Shekari, Faezeh Asghari, Navideh Haghnavaz, Dariush Shanehbandi, Vahid Khaze, Behzad Baradaran, Tohid Kazemi*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 19 , Issue 3 , 2019

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Graphical Abstract:


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.

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Article Details

VOLUME: 19
ISSUE: 3
Year: 2019
Page: [304 - 309]
Pages: 6
DOI: 10.2174/1871520619666181213110258
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