This study aimed to investigate the effects of miR-34a and the possible underlying molecular mechanisms on human keratinocyte cell (HaCaT) proliferation and apoptosis. We used keratinocyte growth factor (KGF) to induce HaCaT cell proliferation. Then, HaCaT cells were transfected with miR-34a mimic, si-miR-34a, and control (siNC). The cell proliferative and invasive capacities were determined using a 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2Htetrazolium bromide (MTT) colorimetric assay and a Matrigel invasion chamber assay, respectively. Cells apoptosis was detected by Annexin V-FITC/PI Kit. Besides, the expression changes in Smac-mediated mitochondrial apoptotic pathway key proteins were measured by Western blot analysis. These key proteins included antiapoptotic protein (Bcl-2) and pro-apoptotic proteins (Cyt C, cleaved/pro-caspase-3, and cleaved/pro-caspase-9). HaCaT cell proliferation increased with increase in the concentration of KGF, with maximum proliferation at 20 ng/mL concentration (P<0.01). miR-34a overexpression significantly suppressed HaCaT cell proliferation (P< 0.05) and increased apoptosis (P< 0.05). Moreover, miR-34a overexpression significantly down-regulated the expression of Bcl-2 (P< 0.05), and up-regulated the expression of Cyt C (P< 0.01), cleaved-caspase-3 (P< 0.01), and cleaved-caspase- 9 (P< 0.05). However, the effects of miR-34a suppression on HaCaT cells proliferation, apoptosis and on these four protein expressions were completely opposite to those found out in miR-34a overexpression. miR-34a overexpression inhibits human keratinocyte (HaCaT cells) proliferation and induces apoptosis through activation of Smac-mediated mitochondrial apoptotic pathway. Therefore, miR-34a might be used as a therapeutic target for treating psoriasis.
