A previous study demonstrated that nicotinamide N-methyltransferase (NNMT) is upregulated in the tissues of patients with prostate cancer (PCa); however, the specific underlying mechanism of this remains unclear. To begin with, the expression of NNMT was investigated in the peripheral blood of patients with PCa and of healthy control subjects. The results indicated that the expression level of NNMT was elevated in the peripheral blood and tissues of patients with PCa. Furthermore, the overexpression of NNMT enhanced PC-3 cell viability, invasion and migration capacity. Additionally, the overexpression of NNMT significantly increased the mRNA level of sirtuin 1 (SIRT1) in PC-3 cells. In addition, nicotinamide treatment significantly suppressed the expression of SIRT1 even in PC-3 cells transfected with adeno-associated virus-NNMT. Furthermore, the PC-3 cell invasion capacity was notably decreased by the nicotinamide treatment; however, such effects were largely abolished by the overexpression of NNMT in PC-3 cells. These data indicated that NNMT enhanced PC-3 cell migration and invasion mainly by regulating SIRT1 expression. In summary, the present study indicated that NNMT is an important regulator of SIRT1 expression in PC-3 cells and may be a potential therapeutic target for PCa.

Abstract. Activating transcription factor 2 (ATF2) is a member of the cAMP response element binding protein family that heterodimerizes and activates other transcription factors involved in stress and DNA damage responses, growth, differentiation and apoptosis. ATF2 has been investigated as a potential carcinogenic biomarker in certain types of cancer, such as melanoma. However, its function and clinical significance in non-small cell lung cancer (NSCLC) has not been well studied. Therefore, the present study aimed to analyze the association between ATF2/phosphorylated (p)-ATF2 expression and NSCLC malignant behavior, and discuss its clinical significance. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression of ATF2 in NSCLC cell lines and fresh NSCLC tissue samples. In addition, immunohistochemistry (IHC) was performed to identify the location and expression of ATF2 and p-ATF2 (threonine 71) in paraffin-embedded sections of NSCLC and adjacent normal tissue. The results demonstrated that ATF2 was markedly overexpressed in the NSCLC cells and significantly overexpressed in the fresh NSCLC tissues compared with the control cells and samples (86 paraffinembedded tissue sections), respectively (P<0.01). Further data demonstrated that ATF2 expression levels were significantly increased in tumor tissues compared to normal tissues and ATF2 was located in the cytoplasm and nucleus. ATF2 expression was closely associated with adverse clinical characteristics such as TNM stage (P=0.002), tumor size (P=0.018) and metastasis (P=0.027). In addition, nuclear p-ATF2 staining was positive in 65/86 samples of NSCLC. Furthermore, the Kaplan-Meier analysis indicated that patients with high levels of ATF2 and p-ATF2 expression had a significantly shorter overall survival compared with patients exhibiting a low expression (P<0.01 and P<0.05, respectively). Subsequent in vitro experiments revealed that cell growth decreased following knockdown of ATF2 expression using RNA interference, indicating that ATF2 may suppress cell proliferation. Taken together, the results of the present study demonstrated that ATF2 and p-ATF2 were significantly overexpressed in NSCLC tissues, and ATF2 and p-ATF2 overexpression predicted significantly worse outcomes for patients with NSCLC.

Long noncoding RNAs (lncRNAs) play a crucial role in several malignances, involving nasopharyngeal carcinoma (NPC), a heterogeneous disease. This study investigated mechanism of serine/arginine repetitive matrix protein 2‐alternative splicing (SRRM2‐AS) in NPC cell proliferation, differentiation, and angiogenesis. Initially, differentially expressed lncRNAs were screened out via microarray analysis. Vascular endothelial growth factor (VEGF) protein positive rate and microvessel density (MVD) were determined in NPC and adjacent tissues. NPC CNE‐2 cells were treated with a series of vector and small interfering RNA to explore the effect of SRRM2‐AS in NPC. The target relationship between myosin light chain kinase (MYLK) and SRRM2‐AS was verified. Levels of SRRM2‐AS, MYLK, cGMP, PKG, VEGF, PCNA, Ki‐67, B‐cell lymphoma‐2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), and Caspase 3 were determined after transfection. Finally, the effect of SRRM2‐AS on cell proliferation, colony formation, angiogenesis, cell cycle, and apoptosis in NPC was evaluated. SRRM2‐AS was highly expressed and MYLK was poorly expressed in NPC tissues. VEGF protein positive rate and MVD were elevated in NPC tissues. MYLK was confirmed to be a target gene of SRRM2‐AS. Silencing of SRRM2‐AS elevated levels of MYLK, cGMP, PKG, Bax, and Caspase 3, but decreased levels of VEGF, PCNA, Ki‐67, and Bcl‐2. Especially, silencing of SRRM2‐AS suppressed cell proliferation, colony formation and angiogenesis, blocked cell cycle, and enhanced cell apoptosis in NPC. Our results suggested that silencing of SRRM2‐AS protected against angiogenesis of NPC cells by upregulating MYLK and activating the cGMP‐PKG signaling pathway, which provides a new target for NPC treatment.

The screened aggressive cancer-associated DEG (PTX3, SNAI2, IL-8/6, SPARC, MMP-1 and Rab25) and significant pathways (calcium signaling pathway, tyrosine metabolism, alanine, aspartate and glutamate metabolism) give us new insights into the mechanism of aggressive breast cancer cells, and these DEG may become promising target genes in the treatment of metastatic breast cancer.

Primary liver cancer is often manifested in the form of hepatocellular carcinoma (HCC) stemming from liver hepatocytes and ranks as the 4 th most common malignancy worldwide. 1,2 HCC remains a leading cause of morbidity and mortality in the western world in regions such as the United States, which has been reported to have the largest increase in cancer-related deaths over the past 2 decades, resulting