Mir-16 and mir-34a collaborate in breast tumor suppression

Recent investigations have shown tumor suppressive roles for miR-16 and miR-34a. It also seems that miR-16 and miR-34a share some feature in regards to targeting cancer cell signaling pathways whichthey control. Therefore, in this study we aimed to more scrutinize whether exogenous induction of mature miR-34a and miR-16 can collaborate in induction of apoptosis, cell cycle arrest and inhibition ofinvasion and migration in human breast cancer cells. MDA-MB-231 and SK-BR-3 human breast cancer cell lines were cultured and transfected twice with hsa-miR-16 and hsa-miR-34a mimics individually orin combination during a 7-day culture period. At the 7th day post-transfection, the cells were analyzed for apoptosis rate and cell cycle indices by flow cytometry. Also expression of several invasion andEMT markers was evaluated at gene and protein levels by quantitative real-time PCR and western blot, respectively. Assessment of invasiveness and migratory potential of the transfected cells was performed using 3D-spheroid assay and wound healing assay, respectively. In both cell lines, miR-16 and miR-34a induced apoptosis, cell cycle arrest, and also suppressed invasion and migration. Some of these effects, like cell cycle arrest and induction of apoptosis seemed to be significantly larger when using both miRNAs than when using them individually for transfection of the cells. Our results are indicating that miR-16 and miR-34a can collaborate in tumor suppression. Since it has been shown that miR-16 and miR-34a are either deleted or down-regulated in breast tumors and especially in those with more invasive nature, administration of these miRNAs and especially a combination of both miRNAs may have potential for treatment of invasive breast tumors

کلیدواژه ها:

Breast Cancer ، Gene and Cancer ، Cell and Cancer ، Cancer Genetics ، Targeted Cancer Therapy ، Drugs and Cancer