Overexpression of lncRNA IRAIN restrains the progression and Temozolomide resistance of glioma via repressing IGF-1R-PI3K-NF-κB signaling pathway.

BACKGROUND: Increasing studies have found that long noncoding RNAs (lncRNAs) contribute to regulating tumor progression. This study explores the expression characteristics, effects, and related mechanisms of lncRNA IGF1R antisense imprinted non-protein coding RNA (IRAIN) in glioma. METHODS: Quantitative real-time PCR (qRT-PCR) was implemented to testify the IRAIN profile in glioma tissues and paracancerous tissues, and the link between the IRAIN level and the clinicopathological indicators of glioma was analyzed. IRAIN overexpression and knockdown cell models were constructed in glioma cells. Cell proliferation was verified by the colony formation experiment, while flow cytometry was implemented to monitor apoptosis. Transwell assay was performed to examine cell invasion and migration. Western blot (WB) was adopted to compare the profiles of the apoptosis-related proteins (Bax, Bcl2, and Caspase3) and IGF-1R-PI3K-NF-κB pathway. RESULTS: IRAIN was down-regulated in glioma tissues (compared with adjacent normal tissues), and the low IRAIN expression was significantly linked with the larger tumor volume and higher pathological stages. Functionally, overexpressing IRAIN abated glioma cell proliferation, invasion, and migration, promoted apoptosis, and attenuated IGF-1R-PI3K-NF-κB expression and temozolomide (TMZ) resistance, which was also confirmed in the xenograft tumor experiment. The WB result showed that overexpressing IRAIN inactivated the IGF-1R-PI3K-NF-κB pathway. Additionally, the IGF-1R knockdown model was established in U251 cells. Si-IGF-1R induced cell proliferation inhibition, promoted cell death, and reduced cell migration and TMZ resistance, whereas Si-IGF-1R+IRAIN group showed no additional effects on glioma cells compared with the Si-IGF-1R group. CONCLUSION: IRAIN repressed glioma development and TMZ resistance by inactivating the IGF-1R-PI3K-NF-κB axis.

Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice.

BACKGROUND: Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models. METHODS: We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group. RESULTS: We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 109/L at the 28th day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF4:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] µmol/L) at the 28th day, particularly those injected with 1.5 mg/kg NaYbF4:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney. CONCLUSION: The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.