High mobility group protein N2 inhibits the progression of hepatocellular carcinoma and the related molecular mechanisms.

High mobility group protein N2 (HMGN2) related pathways are involved in chromatin regulation/acetylation. It has been reported to be involved in several types of cancers. A recent sequencing study suggested that HMGN2 might be involved in the progression of hepatocellular carcinoma (HCC). This study aimed to explore the role of HMGN2 in HCC, which has been proven to be involved in the development of HCC. In this study, we collected clinical samples and cultured normal hepatocytes and hepatocellular carcinoma cell lines to detect HMGN2 expression levels using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Subsequently, to determine the role of HMGN2 in HCC, HMGN2 was overexpressed in HCC cell lines. MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide) assay was used to detect the cell proliferative capacity, and proliferation-related proteins were detected by RT-qPCR and western blot assay. To observe the effect of HMGN2 on cell migration and invasion capacity, Transwell assay was performed. Then, cell apoptosis was detected by flow cytometry, and caspase3 and cleaved-caspase3 were detected using western blot assay. Finally, EMT (epithelial to mesenchymal transition)-related proteins, and matrix metalloproteinase-2 (MMP-2) and MMP-9 expression were detected by RT-qPCR and western blot assay. HMGN2 expression was decreased in HCC tissues as well as in HCC cell lines. After overexpression of HMGN2, MTT results suggested that cell proliferation was decreased, and flow cytometry results showed that the apoptosis level was increased and ki-67 and proliferating cell nuclear antigen (PCNA) expression levels were decreased. On the contrary, cleaved-caspase 3 expression level was increased. HCC cells overexpressing HMGN2 showed a drastic reduction in the number of migrating and invading cells, and the expression levels of MMP-2 and MMP-9 were significantly decreased. Finally, E-cadherin expression was elevated in HCC cells transfected with the HMGN2-plasmid, while N-cadherin showed the opposite result. HMGN2 expression was significantly decreased in patients with HCC. HMGN2 inhibits the malignant behavior of HCC cells and is a potential therapeutic target for HCC.