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Background: Long non-coding RNAs (lncRNAs) have been reported to have a crucial impact on the pathogenesis of acute myeloid leukemia (AML). Cuproptosis, a copper-triggered modality of mitochondrial cell death, might serve as a promising therapeutic target for cancer treatment and clinical outcome prediction. Nevertheless, the role of cuproptosis-related lncRNAs in AML is not fully understood., Methods: The RNA sequencing data and demographic characteristics of AML patients were downloaded from The Cancer Genome Atlas database. Pearson correlation analysis, the least absolute shrinkage and selection operator algorithm, and univariable and multivariable Cox regression analyses were applied to identify the cuproptosis-related lncRNA signature and determine its feasibility for AML prognosis prediction. The performance of the proposed signature was evaluated via Kaplan-Meier survival analysis, receiver operating characteristic curves, and principal component analysis. Functional analysis was implemented to uncover the potential prognostic mechanisms. Additionally, quantitative real-time PCR (qRT-PCR) was employed to validate the expression of the prognostic lncRNAs in AML samples., Results: A signature consisting of seven cuproptosis-related lncRNAs (namely NFE4, LINC00989, LINC02062, AC006460.2, AL353796.1, PSMB8-AS1, and AC000120.1) was proposed. Multivariable cox regression analysis revealed that the proposed signature was an independent prognostic factor for AML. Notably, the nomogram based on this signature showed excellent accuracy in predicting the 1-, 3-, and 5-year survival (area under curve = 0.846, 0.801, and 0.895, respectively). Functional analysis results suggested the existence of a significant association between the prognostic signature and immune-related pathways. The expression pattern of the lncRNAs was validated in AML samples., Conclusion: Collectively, we constructed a prediction model based on seven cuproptosis-related lncRNAs for AML prognosis. The obtained risk score may reveal the immunotherapy response in patients with this disease., (© 2023. The Author(s).)

Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. The long-term survival rate of OS patients is stubbornly low mainly due to the chemotherapy resistance. We therefore aimed to investigate the antitumoral effects and underlying mechanisms of proanthocyanidin B2 (PB2) on OS cells in the current study. The effect of PB2 on the proliferation and apoptosis of OS cell lines was assessed by CCK-8, colony formation, and flow cytometry assays. The target gene and protein expression levels were measured by qRT-PCR and Western blotting. A xenograft mouse model was established to assess the effects of PB2 on OS proliferation and apoptosis in vivo. Results from in vitro experiments showed that PB2 inhibited the proliferation and induced apoptosis of OS cells, and also increased the expression levels of apoptosis-related proteins. Moreover, PB2 induced OS cell apoptosis through suppressing the PI3K/AKT signalling pathway. The in vivo experiments further confirmed that PB2 could inhibit OS tumour growth and induce its apoptosis. Taken together, these results suggested that PB2 inhibited the proliferation and induced apoptosis of OS cells through the suppression of the PI3K/AKT signalling pathway., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Hypoxia‑induced apoptosis occurs in various diseases. Cobalt chloride (CoCl2) is a hypoxia mimic agent that is frequently used in studies investigating the mechanisms of hypoxia. Nuclear respiratory factor‑1 (NRF‑1) is a transcription factor with an important role in the expression of mitochondrial respiratory and mitochondria‑associated genes. However, few studies have evaluated the effects of NRF‑1 on apoptosis, particularly with regard to damage caused by CoCl2. In the present study, the role of NRF‑1 in mediating CoCl2‑induced apoptosis was investigated using cell viability analysis, flow cytometry, fluorescence imaging, western blotting analysis, energy metabolism analysis and reverse transcription‑quantitative polymerase chain reaction. The present results revealed that the apoptosis caused by CoCl2 could be alleviated by NRF‑1. Furthermore, overexpression of NRF‑1 increased the expression of B‑cell lymphoma‑2, hypoxia inducible factor‑1α and NRF‑2. Also, cell damage induced by CoCl2 may be associated with depolarization of mitochondrial membrane potential, and NRF‑1 suppressed this effect. Notably, the oxygen consumption rate (OCR) was reduced in CoCl2‑treated cells, whereas overexpression of NRF‑1 enhanced the OCR, suggesting that NRF‑1 had protective effects. In summary, the present study demonstrated that NRF‑1 protected against CoCl2‑induced apoptosis, potentially by strengthening mitochondrial function to resist CoCl2‑induced damage to H9C2 cells. The results of the present study provide a possible way for the investigation of myocardial diseases.