Restoration of miR-۴۵۱a-۵p/miR-۳۴a-۵p could suppress the proliferation and migration of human breast cancer cells through Wnt/β- catenin and ERK/P-ERK signaling pathways

MicroRNAs (miRNAs) are a class of small non-coding RNAs of ۲۱–۲۵ nucleotides in length and display an essential role in regulating cancer initiation, development, and progression. Breast cancer (BC) is the most commonly detected malignancy in women, and it is one of the main motives of death worldwide. In this study, the impacts of microRNA-۴۵۱a-۵p and miR-۳۴a-۵p (tumor suppressors), individually and combined, transfections were conducted on the apoptosis, proliferation, and migration of breast cancer cells in vitro. For carrying out this research, malignant breast cancer cells (MDA-MB-۲۳۱) were transfected with miR-۴۵۱a-۵p and miR-۳۴a-۵p mimics. Then, the cytotoxicity, apoptosis, proliferation, migration and, the protein and gene expression of caspase-۳, caspase-۸, MMP۹, ROCK, vimentin, c-Myc of the cancer cells were assessed by MTT, flow cytometry, q-RT-PCR (expression levels of caspase-۳, caspase-۸, MMP۹, ROCK, vimentin, c-Myc genes), wound healing, and western blot assays. The resluts indicated that the miR-۳۴a-۵p and miR-۴۵۱a-۵p could additionally induce apoptosis and cell cycle arrest in the sub-G۱-phase, repress the proliferation and migration in the breast cancer cells, and could also decrease β- catenin, ERK/P-ERK protein expressions. The present data documented that restoring tumor suppressor miR-۴۵۱/miR-۳۴ in vitro strongly induced the programmed cell death and obviously inhibited the cell proliferation and migration in human breast cancer cells. Taken to gather, miR-۴۵۱a and miR-۳۴a have a considerable role in breast cancer cell proliferation and migration ability via Wnt/β-catenin and ERK/P-ERK signaling pathways. Therefore, the simultaneous restoration of the presented tumor suppressor miRNAs may be proposed as a valuable and potential therapeutic strategy in breast cancer treatment. However, further study should be meaningful.

کلیدواژه ها:

Breast cancer ، miR-۴۵۱ ، miR-۳۴ ، Migration ، Apoptosis