Let-7d and miR-185 Impede Epithelial-Mesenchymal Transition by Downregulating Rab25 in Breast Cancer

Document Type : Research Articles

Authors

1 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

2 Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

3 Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

4 Department of Medical Biotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

5 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

Objective: MicroRNAs (miRNAs) expression has deregulated in several cancer types including breast cancer (BC). The present study aims at investigating the role, mechanism, clinical value of let-7d and miR-185 in BC, and the possible correlation these miRNAs with Rab25. Materials and Methods: Tumor samples as well adjacent normal tissues (ANT) were acquired from fresh surgical specimens from 110 patients and the expression levels of let-7d, miR-185, Rab25, and snail were evaluated using real-time PCR. The immunohistochemical (IHC) process and western blot were done to detect the level of Rab25 and Snail protein expression in BC samples. Results: By comparing miRNAs expression profiles in clinical tissues of 110 patients using real-time PCR, let-7d, and miR-185 expression were dramatically downregulated in BC tissues (P < 0.05). Tumor size, stage, and lymph node metastasis were significantly related to miRNAs expression. Based on qRT-PCR and bioinformatics database analyses, we also recognized Rab25 as a possible target of miR-185 and let-7d. Rab25 expression was enhanced in BC cells and associated inversely with the expression level of mentioned miRNAs. qRT-PCR, immunohistochemistry, and western blot studies verified that Rab25 upregulation increased the levels of the snail, that key transcription factor of epithelial-mesenchymal transition (EMT). Conclusion: These findings demonstrated that let-7d and miR-185 inhibited EMT by targeting Rab25 expression in BC. Therefore, targeting the let-7d and miR-185/Rab25 interaction may offer new therapeutic opportunities for treating BC patients.
 

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Volume 22, Issue 1
January 2021
Pages 305-313
  • Receive Date: 21 September 2020
  • Revise Date: 25 December 2020
  • Accept Date: 23 January 2021
  • First Publish Date: 23 January 2021