Inhibitory effect of miR342 on the progression of triple-negative breast cancer cells in vitro and in the mice model

Abstract

Introduction: Breast cancer is the most common cancer in women worldwide, and the triple-negative subtype is the most invasive, with limited therapeutic options. Since miRNAs are involved in many cellular processes, they harbor great value for cancer treatment. Therefore, in this study, we have investigated the anti-proliferative and anti-invasive roles of miR342 in 4T1 triple-negative cells in vitro and also studied the effect of this miRNA on tumor progression and the expression of its target genes in vivo. Methods: 4T1 cells were transduced with conditioned media of miR342-transfected Hek-LentiX cells. MTT and clonogenic assays were used to assess the viability and colony-forming ability of 4T1 cells. Apoptosis and invasion rates were respectively evaluated by annexin/7-AAD and wound healing assays. At last, in vivo tumor progression was evaluated using H&E staining, real-time PCR, and immunohistochemistry. Results: The viability of transduced-4T1 cells reduced significantly 48 hours after cell seeding and colony forming ability of these cells reduced to 50% of the control group. Also, miR342 imposed apoptotic and anti-invasive influence on these cells in vitro. A 30-day follow-up of the breast tumor in the mice model certified significant growth suppression along with reduced mitotic index and tumor grade in the treatment group. Moreover, decreased expression of Bcl2l1, Mcl1, and ID4, as miR342 target genes, was observed, accompanied by reduced expression of VEGF and Bcl2/Bax ratio at the protein level. Conclusion: To conclude, our data support the idea that miR342 might be a potential therapeutic target for the treatment of triple-negative breast cancer (TNBC).

Keywords

• triple-negative breast cancer
• mir342
• tumor progression
• proliferation
• invasion