hsa-miR-34a-5p potentiates cytarabine-mediated cell cycle arrest in MDA-MB-231 cells: a novel combination therapy.

Dysregulated cell cycle progression has been implicated in cancer development. Cytarabine can interfere with the S phase of the cell cycle; however, tumoral cells can develop chemoresistance. Specific tumor-suppressive microRNAs (miRs) replacement can arrest the cell cycle and enhance chemosensitivity. Herein, we investigated the effect of hsa-miR-34a-5p replacement and cytarabine on the cell cycle, chemosensitivity, and migration of MDA-MB-231 cells. Our in-silico results have shown that hsa-miR-34a-5p has considerable interactions with β-catenin, CDK4, CDK6, and cyclin-D1; therefore, hsa-miR-34a-5p replacement could arrest cell cycle at the sub-G1 phase. Our in vitro results have indicated that monotherapies with hsa-miR-34a-5p replacement and cytarabine can substantially arrest the cell cycle at the sub-G1 phase; however, the maximal cell cycle arrest has been observed with the combined therapy. Ectopic overexpression of hsa-miR-34a-5p has remarkably enhanced the chemosensitivity of MDA-MB-231 cells. Also, the combined therapy has considerably suppressed the migration of MDA-MB-231 cells compared to the monotherapies. Although the combination therapy has not remarkably decreased the expression of CDK4, CDK6, and cyclin-D1 compared to monotherapy with cytarabine, the combination therapy has substantially downregulated β-catenin expression compared to monotherapy with cytarabine. Overall, this combination therapy is a promising approach to arresting the cell cycle and migration of MDA-MB-231 cells.