The P2X7 receptor, an ATP‐gated ion channel, is critical for cancer cell growth, invasiveness, and angiogenesis. Previous studies indicate that P2X7 regulates osteoblast proliferation and osteodeposition and that high P2X7 expression has a pro‐growth effect in osteosarcoma. However, how it functions in osteosarcoma cell growth and metastasis is not clear. Thus, we elucidated molecular mechanisms of P2X7‐dependent positive regulation of osteosarcoma cell proliferation, invasion, migration, epithelial to mesenchymal transition (EMT), and angiogenesis using in vitro and in vivo models. We confirm that P2X7 is highly‐expressed in human osteosarcoma tumor tissues and HOS/MNNG, MG63, U2OS, SW1353 and SAOS‐2 cell lines. P2X7 receptor stimulation enhanced HOS/MNNG and SAOS‐2 cell proliferation, migration and invasion; but knockdown of P2X7 expression or receptor inhibition had opposite effects. P2X7 positively regulated glycogen content, epithelial to mesenchymal transition and stemness of HOS/MNNG cells. P2X7 activation promoted PI3K/Akt/GSK3β/β‐catenin and mTOR/HIF1α/VEGF signaling, thereby mediating pro‐tumor effects of osteosarcoma cells. Consistent with data from in vitro experiments, systemic administration of P2X7 agonist induced tumor growth, metastasis and tumor‐associated bone destruction in osteosarcoma‐bearing nude mice, whereas a P2X7 antagonist reversed these effects. Thus, the P2X7 receptor participates in regulation of osteosarcoma growth and metastasis and we offer evidence that P2X7 may be a promising therapeutic target for treating osteosarcoma.

Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases.

Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents. In this study, we demonstrated an important role of HS in priming for LPS-induced lung endothelial cell (EC) pyroptosis. We showed that LPS through TLR4 activates Nlrp3 (NACHT, LRR, and PYD domains containing protein 3) inflammasome in mouse lung vascular EC, and subsequently induces caspase-1 activation. However, HS induced release of high-mobility group box 1 (HMGB1), which acting through the receptor for advanced glycation end products initiates EC endocytosis of HMGB1, and subsequently triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. These HS-induced events enhance LPS-induced EC pyroptosis. We further showed that lung vascular EC pyroptosis significantly exaggerates lung inflammation and injury. The present study explores a novel mechanism underlying HS-primed ALI and thus presents a potential therapeutic target for post-HS ALI.

Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts shown to play important roles in tumourigenesis and tumour progression. Our study aimed to examine expression of the lncRNA MAGI2-AS3 in breast cancer and to explore its function in cancer cell growth. First, MAGI2-AS3 expression levels in clinical samples and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The functional significance of MAGI2-AS3 in cancer cell proliferation and apoptosis was then examined in vitro. Our results showed MAGI2-AS3 to be down-regulated in breast cancer tissues compared to normal adjacent tissues. Moreover, MAGI2-AS3 markedly inhibited breast cancer cell growth and increased expression of Fas and Fas ligand (FasL). In conclusion, our data suggest that MAGI2-AS3 expression is decreased in breast cancer and that MAGI2-AS3 plays an important role as a tumour suppressor by targeting Fas and FasL signalling. These results provide new insight into novel clinical treatments for breast cancer.

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Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though studies have implicated the roles of microRNAs in pancreatic cancer progression, little is known about the role of miR-613 in pancreatic cancer. In the present study, the expression of miR-613 was down-regulated in pancreatic cancer tissues and cancer cell lines. Down-regulation of miR-613 was positively correlated with tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall survival in patients with pancreatic cancer. Overexpression of miR-613 suppressed cell proliferation, invasion and migration, and induced cell apoptosis and cell cycle arrest at G0/G1 phase in pancreatic cancer cells. Bioinformatics analysis, luciferase reporter assay and rescue experiments showed that notch3 was a direct target of miR-613. MiR-613 was inversely correlated with notch3 expression in pancreatic cancer tissues. The long non-coding RNA, HOX transcript antisense RNA (HOTAIR) was up-regulated in both pancreatic cancer tissues and cancer cell lines, and HOTAIR suppressed the expression of miR-613 via functioning as a competing endogenous RNA. In vivo studies showed that stable overexpression of miR-613 or knock-down of HOTAIR suppressed tumor growth and also reduced the expression of notch3. In conclusion, these results suggest that HOTAIR functions as a competing endogenous RNA to regulate notch3 expression via sponging miR-613 in pancreatic cancer.

Osteosarcoma is the most common primary bone malignancy in adolescents. Its high propensity to metastasize is the leading cause for treatment failure and poor prognosis. Although the research of osteosarcoma has greatly expanded in the past decades, the knowledge and new therapy strategies targeting metastatic progression remain sparse. The prognosis of patients with metastasis is still unsatisfactory. There is resonating urgency for a thorough and deeper understanding of molecular mechanisms underlying osteosarcoma to develop innovative therapies targeting metastasis. Toward the goal of elaborating the characteristics and biological behavior of metastatic osteosarcoma, it is essential to combine the diverse investigations that are performed at molecular, cellular, and animal levels from basic research to clinical translation spanning chemical, physical sciences, and biology. This review focuses on the metastatic process, regulatory networks involving key molecules and signaling pathways, the role of microenvironment, osteoclast, angiogenesis, metabolism, immunity, and noncoding RNAs in osteosarcoma metastasis. The aim of this review is to provide an overview of current research advances, with the hope to discovery druggable targets and promising therapy strategies for osteosarcoma metastasis and thus to overcome this clinical impasse.

Objective: Nasopharyngeal carcinoma is one of the leading malignancies with obscure etiology. Circulating tumor cells have been showed to intimately correlate with characteristics in different kinds of cancer. But links between circulating tumor cells and nasopharyngeal carcinoma were still lacking. Therefore, we explored circulating tumor cells' distribution in nasopharyngeal carcinoma and their possible associations with nasopharyngeal carcinoma. Methods: Firstly, we found that the positive ratio of circulating tumor cells is extremely high in four stages of nasopharyngeal carcinoma. Meanwhile, positive ratios of mesenchymal circulating tumor cells were higher in early stages of nasopharyngeal carcinoma. Apart from epithelial circulating tumor cells, total, hybrid and mesenchymal circulating tumor cells were correlated with nasopharyngeal carcinoma clinical stage. Results: Our results showed that hybrid and mesenchymal circulating tumor cells were associated with nasopharyngeal carcinoma metastasis (both distant and lymph node) and smoking. Meanwhile, hybrid circulating tumor cells expressed the highest Epstein-Barr virus proteins and deoxyribonucleic acid in three types of circulating tumor cells. Moreover, we found that Epstein-Barr virus proteins viral-caspid antigen-immunoglobulin A (VCA/IgA) and early antigen-immunoglobulin A (EA/IgA), but not Epstein-Barr virus-deoxyribonucleic acid, had a closed association with nasopharyngeal carcinoma metastasis. However, Epstein-Barr virus hallmarks failed to associate with other nasopharyngeal carcinoma characteristics. Furthermore, we confirmed that matrix metalloproteinase 9 existed in circulating tumor cells and expressed most in mesenchymal circulating tumor cells. In addition, matrix metalloproteinase 9-expressed extent in hybrid circulating tumor cells is somewhat different from epithelial and mesenchymal circulating tumor cells in matrix metalloproteinase 9-positive circulating tumor cells. Nevertheless, matrix metalloproteinase 9 had no relationship with other nasopharyngeal carcinoma characteristics. Finally, our results showed that circulating tumor cells were decreased in patients after therapies. carcinoma metastasis. Of note, decreased circulating tumor cells indicated a favorable curative effect in nasopharyngeal carcinoma patients.