circNINL facilitates aerobic glycolysis, proliferation, invasion, and migration in lung cancer by sponging miR-3918 to mediate FGFR1 expression.

Previously characterized as an oncogenic player in breast cancer, the function of circular RNA NINL (circNINL) in lung cancer (LC) remained elusive. This study aimed to delineate the biological role of circNINL in LC and to unveil its potential molecular mechanisms. We discovered elevated expression levels of circNINL and Fibroblast Growth Factor Receptor 1 (FGFR1) concomitant with diminished expression of microRNA-3918 (miR-3918) in LC specimens. Knockdown of circNINL led to a marked decrease in cell proliferation, migration, invasion, and aerobic glycolysis, alongside an upsurge in apoptosis in LC cells. Either downregulation of miR-3918 or overexpression of FGFR1 mitigated the suppressive impact of circNINL knockdown on LC pathogenesis. Mechanistic studies validated that circNINL served as a competitive endogenous RNA for miR-3918, thus influencing FGFR1 expression. Further, in vivo experiments using nude mouse xenograft models underscored that silencing circNINL substantially curtailed tumor growth in LC. Collectively, these findings illuminate that circNINL exacerbates LC malignancy via the miR-3918/FGFR1 axis, a process integrally linked with the activation of aerobic glycolysis.

Association Between Low-Level Blood Cadmium Exposure and Hyperuricemia in the American General Population: a Cross-sectional Study.

Heavy metals, including cadmium, are suspected to increase serum uric acid levels and hyperuricemia in both gender, but the evidences about this are inconclusive. To determine whether serum cadmium in American adults(≥19 years old) is associated with uric acid levels and risk of hyperuricemia, 2620 participants from the US National Health and Nutrition Examination Survey were recruited. Hyperuricemia was defined as a serum UA concentration ≥ 416.4 µmol/L for men and ≥ 356.9 µmol/L for women. Regression analyses were used to analyze the association of cadmium with serum UA and hyperuricemia. The threshold effect explored using two-piecewise linear regression model by the smoothing plot. The overall median of blood cadmium was 0.27 µg/L in men and 0.33µg/L in women. After adjusting for the covariates (race; age; education; BMI; smoke status; alcohol consumption; blood lead; hypertension; diabetes mellitus; hemoglobin; eGFR; triglyceride; and cholesterol), a non-linear relationship between hyperuricemia and cadmium among men was detected; and there was a positive line correlation between them for women (OR = 1.58; 95%CI (1.08, 2.31)). No significant association between uric acid and cadmium in either gender was found. Blood cadmium levels in the range currently considered acceptable were positively associated with increased prevalence of hyperuricemia in women, but inversely associated in men (cadmium <0.77µg/L).

LncRNA MSC-AS1 facilitates lung adenocarcinoma through sponging miR-33b-5p to up-regulate GPAM.

Many reports have indicated that long non-coding RNAs (lncRNAs) are closely associated with the occurrence and development of various cancers. Musculin antisense RNA 1 (MSC-AS1) is a an lncRNA known to act as an oncogene in several types of human cancers; however, its specific function in lung adenocarcinoma (LUAD) is still unclear. For this study, we designed and conducted experiments to clarify the function of the lncRNA MSC-AS1 in LUAD and its underlying mechanisms. We found that the expression of MSC-AS1 was significantly higher in LUAD tissues and cells than that in normal ones. Through loss-of function assays, we confirmed that the proliferation of LUAD cells was significantly restrained by down-regulation of MSC-AS1 and the rate of cell apoptosis was accelerated. The results from our mechanistic experiments showed that MSC-AS1 interacts with microRNA-33b-5p (miR-33b-5p). Moreover, glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) was found to be a direct target gene of miR-33b-5p, and it has similar functions to MSC-AS1. Further, inhibition of miR-33b-5p or overexpression GPAM reversed the inhibitory effects of MSC-AS1 silencing on LUAD cell growth. In short, MSC-AS1 facilitates LUAD progression through sponging miR-33b-5p to up-regulate GPAM.

Forkhead box protein O3a promotes glioma cell resistance to temozolomide by regulating matrix metallopeptidase and ß-catenin.

Glioblastoma multiforme (GBM) is the most common type of malignant brain tumor. GBM is currently treated with temozolomide (TMZ), although patients often exhibit resistance to this agent. Although several mechanisms underlying the resistance of GBM to TMZ have been identified, the combination of these mechanisms is not sufficient to fully account for this phenomenon. Our previous study demonstrated that knocking down the Forkhead box protein O3a (FoxO3a) gene, a member of the FoxO subfamily of transcription factors, resulted in glioma cell sensitization to TMZ, accompanied by reduced levels of nuclear ß-catenin. The aim of the present study was to specify how FoxO3a and ß-catenin are implicated in glioma cell TMZ resistance. Using the U87 and U251 parental cell lines (also designated as sensitive cell lines) and corresponding resistant cell lines (U87-TR and U251-TR, generated by repeated TMZ treatments), coupled with a combined knockdown/overexpression strategy, it was revealed that FoxO3a or ß-catenin overexpression in TMZ-treated U87 and U251 cells markedly increased cellular proliferation; co-expression of both FoxO3a and ß-catenin resulted in the highest increase. Knockdown of either FoxO3a or ß-catenin in U87-TR and U251-TR cells led to a significant decrease in cell viability, which was rescued by the re-expression of FoxO3a in FoxO3a-knockdown cells. Subsequent experiments demonstrated that, in U87-TR and U251-TR cells, FoxO3a knockdown significantly reduced the protein levels of matrix metallopeptidase (MMP)9, while overexpression of FoxO3a in U87 and U251 cells enhanced the nuclear accumulation of ß-catenin, concomitantly with an increase in MMP9 levels. Furthermore, MMP9 knockdown markedly reduced the levels of nuclear ß-catenin. Collectively, the findings of the present study suggest that FoxO3a may regulate the nuclear accumulation of ß-catenin by modulating MMP9 expression, thereby rendering glioblastoma cells resistant to TMZ, and may provide unique molecular insights into the mechanisms underlying the development of TMZ resistance in GBM.

lncRNA PVT1 accelerates progression of non-small cell lung cancer via targeting miRNA-526b/EZH2 regulatory loop.

Biological function of plasmacytoma variant translocation 1 (PVT1) in influencing the progression of non-small cell lung cancer (NSCLC) through Micro ribonucleic acid (miRNA)-526b/EZH2 regulatory loop was elucidated. Relative levels of PVT1 and miRNA-526b in NSCLC tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Prognostic potential of PVT1 in NSCLC was assessed by Kaplan-Meier curves. The interaction among PVT1/miRNA-526b/EZH2 regulatory loop was confirmed by dual-luciferase reporter gene assay. Regulatory effects of PVT1/miRNA-526b/EZH2 axis on viability and wound closure of A549 cells were evaluated by cell counting kit-8 (CCK-8) and wound closure assay, respectively. PVT1 was upregulated in NSCLC tissues, while miRNA-526b was downregulated. PVT1 level was negatively related to that of miR-526 in NSCLC tissues. Worse survival was seen in NSCLC patients expressing high level of PVT1 compared to those with low level. Knockdown of PVT1 attenuated viability and wound closure ability in A549 cells, which were partially reversed after miRNA-526b knockdown. miRNA-526b is the downstream target of PVT1 and its level was negatively regulated by PVT1. EZH2 is the target gene of miRNA-526b. Transfection of miRNA-526b mimic remarkably downregulated EZH2 in A549 cells. Importantly, the attenuated viability and wound closure ability in A549 cells overexpressing miRNA-526b were reversed after EZH2 overexpression. PVT1 is upregulated in NSCLC, and predicts a poor prognosis. PVT1 accelerates the progression of NSCLC via targeting miRNA-526b/EZH2 regulatory loop.