ABSTRACT
Osteosarcoma (OS) is a common primary bone tumor in children and adolescents. Circular RNA (circRNA)-IARS acts as an oncogene in multiple human tumors. However, the circ-IARS function in OS is unclear. This research aimed to elucidate the roles and mechanisms of circ-IARS in OS. In this study, circ-IARS expressions were raised in OS tissues and cells. circ-IARS expressions were closely related to clinical stage and distant metastasis. Furthermore, overall survival rates were reduced in OS patients with high circ-IARS levels. Also, silencing circ-IARS weakened OS cell proliferation and invasion, yet enhanced cell ferroptosis. Mechanistically, circ-IARS targeted miR-188-5p to regulate RAB14 expressions in OS cells. Moreover, circ-IARS knockdown repressed OS cell proliferation, invasion, and induced ferroptosis, yet these impacts were abolished by co-transfection with anti-miR-188-5p or pcDNA-RAB14. Meanwhile, interference with circ-IARS reduced OS cell proliferation, and decreased RAB14 (a member of the RAS oncogene family), GPX4, and xCT (crucial ferroptosis regulators) expressions in vivo. In conclusion, circ-IARS facilitated OS progression via miR-188-5p/RAB14.
Subject(s)
Bone Neoplasms , Ferroptosis , Isoleucine-tRNA Ligase , MicroRNAs , Osteosarcoma , RNA, Circular , rab GTP-Binding Proteins , Animals , Female , Humans , Male , Mice , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation , Disease Progression , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Osteosarcoma/genetics , Osteosarcoma/pathology , Osteosarcoma/metabolism , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism , RNA, Circular/genetics , Isoleucine-tRNA Ligase/genetics , Isoleucine-tRNA Ligase/metabolismABSTRACT
BACKGROUND: Advanced pancreatic cancer (PC) has very poor prognosis with present treatments, thus necessitating continued efforts to find improved therapeutic approaches. Both preclinical and preliminary clinical data indicate that cytokine-induced killer (CIK) cells are an effective tool against various types of solid tumors. Here, we conducted a study to determine whether CIK cell-based therapy (CBT) can improve the outcomes of advanced PC. METHODS: Eighty-two patients with advanced PC, whose predicted survival time was longer than 3 months, were analyzed retrospectively. Of all the patients, 57 individuals were receiving chemotherapy, while the remaining 25 individuals were treated with CBT. RESULTS: The overall survival analysis was based on 48 deaths in the 57 patients in the chemotherapy group (84.2%) and 18 deaths in the 25 patients in the CBT group (72.0%). In the CBT group, the median overall survival time was 13.5 months, as compared to 6.6 months in the chemotherapy group (hazard ratio for death, 0.39; 95% confidence interval, 0.23 to 0.65; p < 0.001). The survival rate was 88.9% in the CBT group versus 54.2% in the chemotherapy group at 6 months, 61.1% versus 12.5% at 12 months, and 38.9% versus 4.2% at 18 months. The disease control rate was 68.0% in the CBT group and 29.8% in the chemotherapy group (p < 0.001). CONCLUSIONS: These results from this retrospective analysis appeared to imply that CBT might prolong survival in these high-risk PC patients. Prospective study is needed to corroborate this observation.
