Restoration of miR-193a-5p and miR-146 a-5p Expression Induces G1 Arrest in Colorectal Cancer through Targeting of MDM2/p53

Saeed Noorolyai; Elham Baghbani; Leili Aghebati Maleki; Amir Baghbanzadeh Kojabad; Dariush Shanehbansdi; Vahid Khaze Shahgoli; Ahad Mokhtarzadeh; Behzad Baradaran

doi:10.15171/apb.2020.017

Restoration of miR-193a-5p and miR-146 a-5p Expression Induces G1 Arrest in Colorectal Cancer through Targeting of MDM2/p53

Adv Pharm Bull. 2020 Jan;10(1):130-134. doi: 10.15171/apb.2020.017. Epub 2019 Dec 11.

Authors

Saeed Noorolyai¹, Elham Baghbani^{1

2}, Leili Aghebati Maleki¹, Amir Baghbanzadeh Kojabad¹, Dariush Shanehbansdi¹, Vahid Khaze Shahgoli¹, Ahad Mokhtarzadeh¹, Behzad Baradaran¹

Affiliations

¹ Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
² Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. Introduction.

Abstract

Purpose: Colorectal cancer (CRC) remains a universal and lethal cancer owing to metastatic and relapsing disease. Currently, the role of microRNAs has been checked in tumorigeneses. Numerous studies have revealed that between the tumor suppressor miRNAs, the reduced expression of miR-146a-5p and -193a-5p in several cancers including CRC tissues are related with tumor progression and poor prognosis of patients. The purpose of this study is to examine the role of miR-146 a-5p and -193 a-5p in CRC cell cycle progression. Methods: The miR-193a-5p and -146 a-5p mimics were transfected into HT-29 CRC cells via jetPEI transfection reagent and their impact was assessed on p53, cyclin B, and NF-kB gene expression. The inhibitory effect of these miRNAs on cell cycle was assessed by flow cytometry. The consequence of miR-193a-5p and miR-146 a-5p on the protein expression level of Murine double minute 2 (MDM2) was assessed by western blotting. Results: miR193a-5p and -146a-5p regulated the expression of MDM2 protein and p53, cyclin B, and NF-kB gene expression in CRC cells. Treatment of HT-29 cells with miRNA-146a-5p and -193a-5p induced G1 cell cycle arrest. Conclusion: The findings of our study suggest that miR146a-5p and -193a-5p may act as a potential tumor suppressor by their influence on cell cycle progression in CRC cells. Thus, miRNA-146a-5p and -193a-5p restoration may be recommended as a potential therapeutic goal in the treatment of CRC patients.

Keywords: Cell cycle; Colorectal cancer; MDM2/p53; Restoration; miRNA-146a-5p; miRNA-193a-5p.