@article { author = {Shahverdi, Mahshid and Amri, Jamal and Karami, Hadi and Baazm, Maryam}, title = {Knockdown of Myeloid Cell Leukemia-1 by MicroRNA-101 Increases Sensitivity of A549 Lung Cancer Cells to Etoposide}, journal = {Iranian Journal of Medical Sciences}, volume = {46}, number = {4}, pages = {298-307}, year = {2021}, publisher = {Shiraz University of Medical Sciences}, issn = {0253-0716}, eissn = {1735-3688}, doi = {10.30476/ijms.2020.83173.1203}, 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.}, keywords = {apoptosis,Etoposide,Lung Neoplasms,Myeloid cell leukemia sequence 1 protein,MicroRNA-101}, url = {https://ijms.sums.ac.ir/article_46988.html}, eprint = {https://ijms.sums.ac.ir/article_46988_f205a36cbcef824eac4126c1a79acb60.pdf} }