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MicroRNA-193a and taxol combination: A new strategy for treatment of colorectal cancer
Authors:Maryam Hejazi  Elham Baghbani  Mohammad Amini  Tayebeh Rezaei  Ayuob Aghanejad  Jafar Mosafer  Ahad Mokhtarzadeh  Behzad Baradaran
Affiliation:1. Department of Genetic, Higher Education Institute of Rab-Rashid, Tabriz, Iran

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;3. Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran;4. Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran;5. Department of Genetic, Higher Education Institute of Rab-Rashid, Tabriz, Iran

Abstract:Micro RNAs (miRNAs) show a considerable promise as a therapeutic agent for combination therapy of colorectal cancer (CRC). Given that, the current study was purposed to explore the potential therapeutic role and underlying mechanism of miR-193a as a promising tumor suppressor in human CRC cell lines in combination with Taxol. Therefore, HT-29 cells with the lowest expression levels of miR-193a were treated with miR-193a mimics and Taxol, separately or in combination. Functional analyses showed that the combination therapy inhibited migration and colony formation of HT-29 cells and arrested the cell cycle at the G1 phase. Moreover, treatment with Taxol reduced cell survival with an increase in mRNA expression of metastasis-related genes caspase-3 and caspase-9, whereas miR-193a transfection alone didn't significantly influence cell viability and apoptosis induction. Quantitative reverse transcription polymerase chain reaction results also revealed that miR-193a replacement decreased the expression levels of c-Myc, MMP-9, vimentin, and ROCK in treatment groups compared to the controls. Therefore, it could be concluded miR-193a inactivates cell migration via suppression of metastasis pathways in CRC and through downregulation of c-Myc, acts as a negative regulator of cell cycle and growth. Then, our findings imply that miR-193a replacement combined with Taxol chemotherapy could be considered as a new potential therapeutic approach for improvement of CRC treatment.
Keywords:colorectal cancer  combination chemotherapy  miRNA-193a  Taxol
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