Abstract
Previous studies have revealed that elevated expression of high mobility group A2 (HMGA2) is closely associated with the occurrence of pituitary adenomas (PAs). The expression of microRNA (miR)-16 is deregulated in PA tissues. Bioinformatics analysis has demonstrated that there is a complementary region between seed region of miR-16 and 3'-untranslated region (3'-UTR) of HMGA2 gene. In the present study, it was investigated whether miR-16 may regulate the expression of HMGA2 and whether it is involved in the pathogenesis of PAs. A total of 52 patients with PAs were recruited. Normal brain tissues obtained from 12 patients with traumatic brain injury were used as controls. The association between miR-16 and HMGA2 was validated using dual-luciferase reporter gene assay. HP75 cells were cultured in vitro and divided into the following groups: miR control, miR-16 mimic, small interfering RNA (si)-negative control, si-HMGA2 and miR-16 mimic+si-HMGA2 groups. The expression of miR-16 and HMGA2 in HP75 cells was determined using qRT-PCR and western blot. Cell proliferation was detected using the Cell Counting Kit-8 assay and apoptosis was detected using the TdT-UTP nick end labeling assay. Compared with normal pituitary tissues, the expression of miR-16 in PA tissues was significantly decreased, while the mRNA and protein levels of HMGA2 were significantly increased. miR-16 targeted the 3'-UTR of HMGA2 gene and regulated the expression of HMGA2. Transfection with siRNAs targeting HMGA2 and/or miR-16 mimics inhibited the expression of HMGA2 and the proliferative ability of HP75 cells, whereas it increased apoptosis of HP75 cells. The downregulation of miR-16 and upregulation of HMGA2 were involved in the pathogenesis of PAs. Thus, it is hypothesized that miR-16 inhibited the proliferation and promoted apoptosis of HP75 cells by inhibiting HMGA2 expression.