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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.

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