Cyr61 (CCN1) is the product of a growth factor–inducible immediate early gene and is involved in cell adhesion, survival, proliferation, and differentiation. Cyr61 is overexpressed in human tumors and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients. Furthermore, we observed that Cyr61 could effectively stimulate Jurkat (T ALL cell lines), Nalm-6 (B ALL cell lines), and primary ALL cell survival. Mechanistically, we showed that Cyr61 stimulated ALL cell survival via the AKT/NF-κB signaling pathways and the consequent up-regulation of Bcl-2. Taken together, our study is the first to reveal that Cyr61 is elevated in ALL and promotes cell survival through the AKT/NF-κB pathway by up-regulating Bcl-2. Our findings suggest that Cyr61 plays an important role in the pathogenesis of ALL.

Surgical resection of hepatocellular carcinoma suffers from a high recurrence rate. Ozone directly kills tumor cells by generating reactive oxygen species in vitro, but its high reactivity and short half-life severely limit its tumor accumulation and penetration for the treatment of tumors in vivo. Herein, a thermoresponsive ozone-enriched spray gel is developed to suppress the tumor recurrence of hepatocellular carcinoma (Huh-7 tumors). Briefly, a perfluorocarbon nanoemulsion (PFTBA@LIP) consisting of a perfluorotributylamine core and a lipid monolayer is fabricated, which is encapsulated in the thermoresponsive hydrogel. Ozone is then dissolved in the nanoemulsion owing to its high affinity to PFTBA (O3/PFTBA@LIP@Gel), which effectively improves its stability. Of note is that O3/PFTBA@LIP@Gel induces both ferroptosis and apoptosis by regulating the expression of relevant genes (GPX4, ACSL4, CDKN1A, etc.) and inducing considerable lipid peroxidation, which significantly reduces the tumor recurrence of the Huh-7 tumor by spraying the gel in the surgical cavity and prolongs the survival of tumor-bearing mice.

Cell-cell fusion is a critical step in osteoclast development, because only after osteoclasts become multinucleated can they efficiently resorb bone. Although recent studies suggest that dendritic cell-specific transmembrane protein (DC-STAMP) may play a key role in the process of fusion of mouse osteoclasts, little information has been available on the role of DC-STAMP in human osteoclasts. In this study, we screened and identified an in vitro-transcribed short-hairpin RNA targeting human DC-STAMP from four candidates and generated a lentivirus vector. Subsequent experiments indicated that this lentiviral transgenic system could effectively transfer into target human osteoclasts, at more than 80 % gene transfer efficiency at multiplicity of infection of 15, and significantly and specifically inhibited DC-STAMP expression at both mRNA and protein levels. We also found that DC-STAMP inhibition by RNAi consequently suppressed fusion and bone resorption of human osteoclasts. In conclusion, these data indicated the lentivirus-mediated RNAi was capable of efficiently suppressing DC-STAMP expression in primary human osteoclasts and inhibiting osteoclastogenesis, demonstrating an essential role of DC-STAMP in the differentiation of human osteoclasts.

Elevated Cyr61 levels have been reported in various malignancies. Elevation of Cyr61 protein levels contributes to the proliferation, metastasis, and chemotherapy resistance of malignant cells. Previously, it was discovered that Cyr61 is elevated in both the plasma and the bone marrow supernatants of patients with acute lymphoblastic leukemia (ALL), promoting ALL cell survival. However, the role of Cyr61 in the chemotherapeutic resistance of ALL cells remains unknown. The aim of the current study was to investigate the role of Cyr61 in regulating ALL cell chemosensitivity to Ara-C. It was found that Cyr61 is overexpressed in bone marrow mononuclear cells from patients with ALL. Increased Cyr61 effectively decreased Ara-C-induced apoptosis of ALL cells, and its function was blocked by the use of the anti-Cyr61 monoclonal antibody 093G9. Furthermore, Cyr61 increased the level of Bcl-2 in Ara-C-treated ALL cells. Mechanistically, it was shown that Cyr61 affected ALL cell resistance to Ara-C partially via the NF-κB pathway. Taken together, the present study is the first, to the best of our knowledge, to reveal that Cyr61 is involved in ALL cell resistance through the NF-κB pathway. The findings support a functional role for Cyr61 in promoting chemotherapy resistance, suggesting that targeting Cyr61 directly or its relevant effector pathways may improve the clinical responses of patients with ALL.