Downregulation of HMGA2 inhibits cellular proliferation and invasion, improves cellular apoptosis in prostate cancer.

Abstract

Prostate cancer is the most commonly diagnosed cancer among men and is the second leading cause of cancer-associated deaths among men in the world. Unfortunately, treatment failures are common due to the metastasis and chemoresistance, but the underlying molecular mechanism remains unclear. Accumulating evidence has indicated that the deregulation of DNA-binding protein High Mobility Group A2 (HMGA2) is associated with the development and progression of cancer. This study aimed to explore the expression of HMGA2 in prostate cancer tissues and its correlation to the clinical pathology of prostate cancer, and to discuss the role of HMGA2 in the development of prostate cancer. The results showed that the expression of HMGA2 messenger RNA (mRNA) in the prostate cancer tissues and cells was significantly higher than that in normal prostate tissues and cells (p < 0.05), and the positive expression rate of HMGA2 mRNA in the prostate cancer tissues from patients with positive lymph node metastasis or with high Gleason grade was significantly higher than that from patients with negative lymph node metastasis or with low Gleason grade (p < 0.05). In order to explore the role of HMGA2 in prostate cancer, the expression of HMGA2 in the human prostate cancer PC3 cell line was downregulated by RNA interference. Then, the changes in proliferation, apoptosis, invasion, and migration of PC3 cells were examined by MTT test, PI staining, Annexin V-FITC staining, and Transwell chamber assay. Results showed that the abilities of proliferation, invasion, and migration were suppressed in HMGA2 knockdown PC3 cells, and the abilities of apoptosis were enhanced in HMGA2 knockdown PC3 cells. The expression of cyclin A and vimentin was downregulated in HMGA2 knockdown PC3 cells, and the expression of caspase 3 and E-cadherin was upregulated in HMGA2 knockdown PC3 cells. Taken together, the overexpression of HMGA2 in prostate cancer might be related to the tumorigenesis, invasion, and metastasis of prostate cancer, the downregulation of HMGA2 could inhibit cellular proliferation, invasion, and metastasis, and improve cellular apoptosis in prostate cancer, which might be a potential target for the treatment of prostate cancer.