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Adv Pharm Bull. 2020;10(4): 595-601.
doi: 10.34172/apb.2020.071
PMID: 33072537
PMCID: PMC7539307
Scopus ID: 85090475121
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Research Article

Restoring of miR-193a-5p Sensitizes Breast Cancer Cells to Paclitaxel through P53 Pathway

Monireh Khordadmehr 1* ORCID logo, Roya Shahbazi 1, Behzad Baradaran 2,3*, Sanam Sadreddini 2, Dariush Shanebandi 2, Khalil Hajiasgharzadeh 2

1 Department of Pathology, Faculty of Veterinary Medicine, University of Tabriz, 51665-1647, Tabriz, Iran.
2 Immunology Research Center, Tabriz University of Medical Sciences, 51666-14761, Tabriz, Iran.
3 Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, 51666-14761, Tabriz, Iran.
*Corresponding Authors: *Corresponding Authors: Monireh Khordadmehr and Behzad Baradaran, Tel: +98 41 36378743; Fax: +98 41 36378744; Email: , Email: baradaranb@tbzmed.ac.ir, Email: khordadmehr@ tabrizu.ac.ir; Email: baradaranb@tbzmed.ac.ir

Abstract

Purpose: Recent evidence presented the important role of microRNAs in health and disease particularly in human cancers. Among those, miR-193 family contributes as a tumor suppressor in different benign and malignant cancers like breast cancer (BC) via interaction with specific targets. On the other hand, it was stated that miR-193 is able to modulate some targets in chemoresistant cancer cells. Therefore, the aim of this study was to evaluate the potential function of miR-193a-5p and paclitaxel in the apoptosis induction by targeting P53 in BC cells.

Methods: At first, miR-193a-5p mimics were transfected to MDA-MB-231 BC cell line which indicated the lower expression level of miR-193a-5p. Subsequently, the transfected cells were treated with paclitaxel. Then, cell viability, apoptosis, and migration were evaluated by MTT, flow cytometry and DAPI staining, and scratch-wound motility assays, respectively. Moreover, the expression levels of P53 was evaluated by qRT-PCR.

Results: The expression level of miR-193a-5p was restored in MDA-MB-231 cells which profoundly inhibited the proliferation (P<0.0001), induced apoptosis (P<0.0001) and harnessed migration (P<0.0001) in the BC cells and more effectiveness was observed in combination with paclitaxel. Interestingly, increased miR-193a-5p expression led to a reduction in P53 mRNA, offering that it can be a potential target of miR-193a.

Conclusion: Taken together, it is concluded that the combination of miR-193a-5p restoration and paclitaxel could be potentially considered as an effective therapeutic strategy to get over chemoresistance during paclitaxel chemotherapy

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Submitted: 12 Nov 2019
Revision: 11 Jan 2020
Accepted: 27 Jan 2020
ePublished: 09 Aug 2020
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