MiR-16 regulates proliferation and apoptosis of pituitary adenoma cells by inhibiting HMGA2.

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.