The high mobility group protein A2 (HMGA2) has been demonstrated as an architectural transcription factor that is associated with pathogenesis of many malignant cancers; however, its role in prostate cancer cells remains largely unknown. To explore whether HMGA2 participates in the development and progression of prostate cancer, small interfering RNA (siRNA) targeted on human HMGA2 was transfected to suppress the HMGA2 expression in prostate cancer PC3 and DU145 cells, and then the cellular biology changes after decreased the expression of HMGA2 was examined. Our results showed that knockdown of HMGA2 markedly inhibited cell proliferation; this reduced cell proliferation was due to the promotion of cell apoptosis as the Bcl-xl was decreased, whereas Bax was up-regulated. In addition, we found that HMGA2 knockdown resulted in reduction of cell migration and invasion, as well as repressed the expression of matrix metalloproteinases (MMPs) and affected the occurrence of epithelial-mesenchymal transition (EMT) in both cell types. We further found that decreased HMGA2 expression inhibited the transforming growth factor-beta (TGF-beta)/Smad signalling pathway in cancer cells. In conclusion, our data indicated that HMGA2 was associated with apoptosis, migration and invasion of prostate cancer, which might be a promising therapeutic target for prostate cancer.

The high-mobility group protein A2 (HMGA2) is an architectural transcription factor that plays a crucial role in the development and progression of various malignant cancers. However, the function of HMGA2 in bladder cancer remains largely unknown. Therefore, we aim to investigate the effect of HMGA2 on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of bladder cancer cells. The expression of HMGA2 in human bladder cancer cells was downregulated by small interfering RNA (siRNA). The protein levels of HMGA2 and other related proteins were detected by Western blotting. The cell proliferation and apoptosis were examined by Cell Counting Kit-8 and flow cytometry, respectively. Transwell migration and invasion assays were performed to assess the effect of HMGA2 on the migration and invasion ability of cells. In conclusion, we found that HMGA2 knockdown markedly inhibited cell proliferation; this reduced cell growth was due to the high apoptosis rate of cells, as Bcl-xl was diminished, whereas Bax was upregulated. Moreover, our results showed that silencing of HMGA2 in cancer cells greatly inhibited the cell migration and invasion, decreased the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), and affected the occurrence of EMT. We further found that decreased HMGA2 expression suppressed the transforming growth factor-β (TGF-β)/Smad and Wnt/β-catenin signaling pathway in bladder cancer cells. These results revealed that HMGA2 played an important role in the progression of bladder cancer and might be a novel target for therapy in human bladder cancer.

High-mobility group nucleosome-binding domain 5 (HMGN5) is a new member of the high-mobility group N (HMGN) protein family that is involved in nucleosomal binding and transcriptional activation. It was first discovered in mouse, and recent studies found that the expressions of HMGN5 in many human cancers were also highly regulated, such as prostate, bladder, breast, and lung and clear cell renal cell carcinoma. Numerous reports have demonstrated that HMGN5 plays significant roles in many biological and pathological conditions, such as in developmental defects, hypersensitivity to stress, embryonic stem cell differentiation, and tumor progression. Importantly, deficiency of HMGN5 has been shown to be linked to cancer cell growth, cell cycle regulation, migration, invasion, and clinical outcomes, and it represents a promising therapeutic target for many malignant tumors. In the present review, we provide an overview of the current knowledge concerning the role of HMGN5 in cancer development and progression.

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