Abstract
Hepatocellular carcinoma (HCC) is correlated with a poor prognosis and high mortality worldwide. Neuronal pentraxin 1 (NPTX1) has been reported to play an oncogenic role in several types of tumors. However, its expression and function in HCC is not yet fully understood. In the present study, we aimed to investigate the clinicopathological significance of NPTX1 in HCC and the underlying mechanisms. We observed that the expression of NPTX1 was decreased significantly in HCC and was associated with tumor size and metastasis in patients. Gain-of-function approaches revealed that NPTX1 suppressed the growth ability of HCC cells and contributed to mitochondria- related apoptosis. Furthermore, mechanistic investigations showed that the AKT (AKT serine/threonine kinase) pathway can regulate the effects of NPTX1 in HCC cells. After blocking the AKT pathway, the action of NPTX1 was greatly increased. In summary, we demonstrated that NPTX1 inhibited growth and promoted apoptosis in HCC via an AKT-mediated signaling mechanism. These findings indicate that NPTX1 is a potential clinical therapeutic target.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer and ranked third among causes of cancer-related mortality worldwide [1,2]
The cells of the LO2 line are normal liver cells, and they expressed more neuronal pentraxin 1 (NPTX1) than did most of the HCC cell lines (QGY-7701, SMMC-7721, PLC/PRF/5, MHCC-97h, HCC-LM3). These results revealed that NPTX1 is down-regulated in HCC
We found that the protein levels of BCL2-associated agonist of cell death (BAD) and BCL2-associated X protein (BAX) were increased in NPTX1-overexpressing SMMC-7721 and MHCC-97h cells relative to control cells
Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer and ranked third among causes of cancer-related mortality worldwide [1,2]. It is urgent to clarify the molecular mechanisms underlying HCC development to identify novel diagnostic markers and promising treatment strategies for improving the prognosis of HCC patients. As a member of the long pentraxin family of proteins, neuronal pentraxin 1 (NPTX1) is mainly expressed in central neurons and plays roles in promoting neurite outgrowth and modulating cellular properties [4,5]. The long pentraxin family has two other members: neuronal pentraxin 2 (NPTX2) and neuronal pentraxin receptor (NPTXR) [6,7]. Previous studies have reported that NPTX1 acts as a mediator of mitochondria-mediated hypoxic–ischemic neuronal injury via a glycogen synthase kinase 3α/β (GSK3α/β)-dependent mechanism [8,9,10]. The expression pattern and biological function of NPTX1 in HCC remain unclear
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