Iranian Journal of Medical Sciences

Document Type: Original Article(s)

Authors

1 Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran

2 Department of Molecular Medicine and Biotechnology, School of Medicine, Arak University of Medical Sciences, Arak, Iran

3 Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran

4 Department of Molecular Medicine and Biotechnology, School of Medicine, Arak University of Medical Sciences, Arak, Iran

5 Department of Anatomy, School of Medicine, Arak University of Medical Sciences, Arak, Iran

Abstract

Background: Studies have shown that myeloid cell leukemia-1 (Mcl-1) is the target gene for MicroRNA -101 (miRNA-101) and decreased levels of miRNA-101 are associated with elevated levels of Mcl-1 and lung cancer survival. The objective of the present study was to investigate the effect of miRNA-101 on the sensitivity of A549 lung cancer cells to etoposide.
Methods: The study was conducted during 2018 and 2019 at Arak University of Medical Sciences, Arak, Iran. The effect of miRNA-101 on Mcl-1 expression was assessed using reverse transcription-quantitative polymerase chain reaction 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT), and trypan blue exclusion assays were performed to determine the effect of treatments on cell survival and proliferation, respectively. The interaction between miRNA-101 and etoposide was evaluated using the combination index analysis of Chou-Talalay. Apoptosis was quantified using ELISA cell death assay. ANOVA and Bonferroni’s tests were used to determine statistical differences between the groups (P<0.05). GraphPad Prism software (version 6.01) was used for data analysis.
Results: The results showed that miRNA-101 clearly inhibited the expression of Mcl-1 and reduced the growth of A549 cells, relative to blank control and negative control miRNA (P<0.05). Transfection of miRNA-101 synergistically enhanced the sensitivity of the A549 cells to etoposide. Apoptosis assay data also showed that miRNA-101 triggered apoptosis and augmented the etoposide-mediated apoptosis.
Conclusion: Up-regulation of miRNA-101 inhibited cell survival and proliferation, and sensitized A549 cells to etoposide by suppressing Mcl-1 expression. MiRNA-101 replacement therapy can be considered as an effective therapeutic strategy in non-small cell lung cancer.

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