Hadis Soltani-Sedeh1, Shiva Irani2, Reza Mirfakhraie3, Masoud Soleimani4. 1. Department of Biology, Science and Research Branch, Islamic Azad University; Stem Cell Technology Research Center, Tehran, Iran. 2. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. 3. Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Abstract
BACKGROUND: MicroRNAs are small noncoding RNAs which modulate gene expression at different levels. It has been shown that downregulation of miR-34a occurs in varieties of cancers including colorectal cancer (CRC). In this study, we investigated the potential tumor inhibitory effects of miR-34a alone or in combination with paclitaxel in CRC cells. MATERIALS AND METHODS: SW480 cells were transduced with lentiviral overexpressed miR-34a. First, using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, the effect of miR-34a induction alone or in combination with paclitaxel on the cell viability and cell proliferation were estimated. Then, the expression level of target genes was measured using quantitative reverse transcription-polymerase chain reaction analysis. Eventually, the role of miR-34a and paclitaxel on cell cycle were determined with flow cytometry. RESULTS: Gene expression analysis showed that miR-34a downregulates the expression of BCL2 and SIRT1 genes at mRNA level. Furthermore, miR-34a has a potential to reduce cell viability and cell cycle arrest at G1 phase. Combination of paclitaxel with overexpression of miR-34a significantly decreased cell viability compared to cell treated with miR-34a or paclitaxel alone. Interestingly, a combination of miR-34a and paclitaxel arrested cell cycle at two phases. CONCLUSION: Our results suggested that combination therapy of miR-34a and paclitaxel could be considered as the potential treatment of CRC.
BACKGROUND: MicroRNAs are small noncoding RNAs which modulate gene expression at different levels. It has been shown that downregulation of miR-34a occurs in varieties of cancers including colorectal cancer (CRC). In this study, we investigated the potential tumor inhibitory effects of miR-34a alone or in combination with paclitaxel in CRC cells. MATERIALS AND METHODS: SW480 cells were transduced with lentiviral overexpressed miR-34a. First, using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, the effect of miR-34a induction alone or in combination with paclitaxel on the cell viability and cell proliferation were estimated. Then, the expression level of target genes was measured using quantitative reverse transcription-polymerase chain reaction analysis. Eventually, the role of miR-34a and paclitaxel on cell cycle were determined with flow cytometry. RESULTS: Gene expression analysis showed that miR-34a downregulates the expression of BCL2 and SIRT1 genes at mRNA level. Furthermore, miR-34a has a potential to reduce cell viability and cell cycle arrest at G1 phase. Combination of paclitaxel with overexpression of miR-34a significantly decreased cell viability compared to cell treated with miR-34a or paclitaxel alone. Interestingly, a combination of miR-34a and paclitaxel arrested cell cycle at two phases. CONCLUSION: Our results suggested that combination therapy of miR-34a and paclitaxel could be considered as the potential treatment of CRC.
Authors: Andrea Angius; Antonio Mario Scanu; Caterina Arru; Maria Rosaria Muroni; Vincenzo Rallo; Giulia Deiana; Maria Chiara Ninniri; Ciriaco Carru; Alberto Porcu; Giovanna Pira; Paolo Uva; Paolo Cossu-Rocca; Maria Rosaria De Miglio Journal: Int J Mol Sci Date: 2021-02-05 Impact factor: 5.923